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torsdag 7 mars 2024

MikroRNA-proteiinien ylössäätyminen ja niiden osuus rintasyövässä; Sovellutuksia syöpähoitoon

 

Review
. 2023;24(6):484-508.
doi: 10.2174/1389450124666230329123409.

MiRNAs Overexpression and Their Role in Breast Cancer: Implications for Cancer Therapeutics

Sau Har Lee  1   2 , Chu Xin Ng  1 , Sharon Rachel Wong  1 , Pei Pei Chong  1
Affiliations
TIIVISTELMÄ  Abstract

MikroRNA-proteiineilla on myriadeja  osia  solujen  erilaisissa biologisissa prosesseissa  ja useimmissa ihmisten syövissä onkin  osoittautunut olevan  assosioitumista   miRNA-geenien  ilmentymän  vikasäätöön.

  • MicroRNAs have a plethora of roles in various biological processes in the cells and most human cancers have been shown to be associated with dysregulation of the expression of miRNA genes. 

miRNA biogeneesi käsittää kaksi vaihtoehtoista reittiä: On kanoninen tie, missä on vaatimuksena     monen proteiinin onnistunut yhteistoiminta  muodostettaessa  miRISC , mikroRNA:n  indusoiva hiljentävä kompleksi , Toinen vaihtoehto ei ole kanoninen. Siihen kuuluu mirtronien-, simtronien- ja agotronien tie, joka  sivuuttelee   kanonista tietä ja eriää kanonisen tien spesifisistä  askelista.

  • MiRNA biogenesis involves two alternative pathways, the canonical pathway which requires the successful cooperation of various proteins forming the miRNA-inducing silencing complex (miRISC), and the non-canonical pathway, such as the mirtrons, simtrons, or agotrons pathway, which bypasses and deviates from specific steps in the canonical pathway. 

 Kypsät mikroRNA:t erittyvät soluista ja niitä kiertelee kehossa sitoutuneena argonaut 2 (AGO2) proteiiniin ja miRISC-kompleksiin tai niitä kulkeutuu vesikkeleissä (rakkuloissa). Tällaiset mikroRNA:t voivat säädellä alavirran kohdegeenejä positiivisella tai negatiivisella säädöllä erilaisin molekulaarisin mekanismein.

  • Mature miRNAs are secreted from cells and circulated in the body bound to argonaute 2 (AGO2) and miRISC or transported in vesicles. These miRNAs may regulate their downstream target genes via positive or negative regulation through different molecular mechanisms. 

 Tässä otsikon katsauksessa keskitytään mikroRNA:itten  osaan ja mekanismeihin  erilaisiin asteisiin edenneissä  rintasyövissä  mukaan luettuna rintasyövän kantasolun muodostus, rintasyövän alkaminen, invasoituminen ja metastasopituminen sekä angiogeneesi.

  • This review focuses on the role and mechanisms of miRNAs in different stages of breast cancer progression, including breast cancer stem cell formation, breast cancer initiation, invasion, and metastasis as well as angiogenesis. 

 Pohdintaan otetaan  myös yksityiskohtia myöten synteettisten anti-sense miRNA oligonukleotidien  hahmottelu, kemiallinen muokkaus ja terapeuttiset sovellukset; samoin  myös synteettiset RNA:n kaltaiset

  • The design, chemical modifications, and therapeutic applications of synthetic anti-sense miRNA oligonucleotides and RNA mimics are also discussed in detail. 

 Antisense-mikroRNA-valmisteiden systeemisen tai paikallisen kohdennetun annon srategioissa mainitaan  polymeeristen ja liposomaalisten nanopartikkeleiden, inorgaanisten nanopartikkeleitten, extrasellulaaristen vesikkeleiden sekä virusvektoreiden ja viruksenkaltaisten partikkeleiden (VLP) käyttö. 

  • The strategies for systemic delivery and local targeted delivery of the antisense miRNAs encompass the use of polymeric and liposomal nanoparticles, inorganic nanoparticles, extracellular vesicles, as well as viral vectors and viruslike particles (VLPs).

 Vaikkakin useita mikroRNAproteiineja on tunnistettu hyvinä ehdokkaina rintasyöpään kohdennettuun  antisense- hahmotteluun ja muitten  synteettisesti modifioitujen oligonukleotidien  hahmotteluun , tarvitsee vielä panostaa  optimaalisimman  antotavan metodin tutkimuksiin, jotta voidaan edetä tieteellisessä  työssä  prekliinisestä vaiheesta  askel eteenpäin.

  • Although several miRNAs have been identified as good candidates for the design of antisense and other synthetic modified oligonucleotides in targeting breast cancer, further efforts are still needed to study the most optimal delivery method in order to drive the research beyond preclinical studies.

Keywords: Cancer therapeutic; anti-sense microRNA; breast cancer; microRNA delivery; oncogenic microRNA; therapeutic microRNA.

PubMed Disclaimer

 

Eräs  tieteellinen työ hiirellä: Myös koeputkitasossa.

 https://pubmed.ncbi.nlm.nih.gov/32345308/

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AGO2 ja Rintasyöpä, onko assosiaatiota= HAKU PubMed 7.3. 2024

 

71 results

Quantifying Argonaute 2 (Ago2) expression to stratify breast cancer.
Casey MC, Prakash A, Holian E, McGuire A, Kalinina O, Shalaby A, Curran C, Webber M, Callagy G, Bourke E, Kerin MJ, Brown JA. BMC Cancer. 2019 Jul 19;19(1):712. doi: 10.1186/s12885-019-5884-x. PMID: 31324173 Free PMC article.
However Ago2 expression and localisation in breast cancer remains undetermined. ...CONCLUSIONS: Quantification of Ago2 improves the stratification of breast cancer and suggests a differential role for Ago2 in breast cance …
The CXCR4-Dependent LASP1-Ago2 Interaction in Triple-Negative Breast Cancer.
Tilley AMC, Howard CM, Sridharan S, Subramaniyan B, Bearss NR, Alkhalili S, Raman D. Cancers (Basel). 2020 Aug 29;12(9):2455. doi: 10.3390/cancers12092455. PMID: 32872485 Free PMC article.
The CXCR4-LASP1 axis is an emerging target in the field of breast cancer metastasis. C-X-C chemokine receptor type 4 (CXCR4) mediates directed cell migration when activated by its cognate ligand CXCL12. ...Our previous proteomics work had revealed several components …
Treatment of breast cancer with autophagy inhibitory microRNAs carried by AGO2-conjugated nanoparticles.
Unal O, Akkoc Y, Kocak M, Nalbat E, Dogan-Ekici AI, Yagci Acar H, Gozuacik D. J Nanobiotechnology. 2020 Apr 28;18(1):65. doi: 10.1186/s12951-020-00615-4. PMID: 32345308 Free PMC article.
These functionalized nanoparticles selectively delivered an effective amount of the microRNA into HER2-positive breast cancer cell lines in vitro and in a xenograft nude mice model of breast cancer in vivo, and successfully blocked autophagy. ...Theref …
Presence of anti-TIF-1gamma, anti-Ro52, anti-SSA/Ro60 and anti-Su/Ago2 antibodies in breast cancer: a cross-sectional study.
Vázquez-Del Mercado M, Martínez-García EA, Daneri-Navarro A, Gómez-Bañuelos E, Martín-Márquez BT, Pizano-Martínez O, Wilson-Manríquez EA, Corona-Sánchez EG, Chavarria-Avila E, Sandoval-García F, Satoh M. Immunopharmacol Immunotoxicol. 2021 Jun;43(3):328-333. doi: 10.1080/08923973.2021.1910833. Epub 2021 Apr 20. PMID: 33876712 Clinical Trial.
As a whole, 14.47% (22/152) of breast cancer patients showed autoantibodies associated with SARD. ...CONCLUSIONS: Autoantibodies to TIF-1gamma were found in two patients with breast cancer without dermatomyositis (DM). More common specificities were au …
MiRNAs Overexpression and Their Role in Breast Cancer: Implications for Cancer Therapeutics.
Lee SH, Ng CX, Wong SR, Chong PP. Curr Drug Targets. 2023;24(6):484-508. doi: 10.2174/1389450124666230329123409. PMID: 36999414 Review.
This review focuses on the role and mechanisms of miRNAs in different stages of breast cancer progression, including breast cancer stem cell formation, breast cancer initiation, invasion, and metastasis as well as angiogenesis. ...Althoug …
RNA interference: Promising approach for breast cancer diagnosis and treatment.
Allahyari E, Velaei K, Sanaat Z, Jalilzadeh N, Mehdizadeh A, Rahmati M. Cell Biol Int. 2023 May;47(5):833-847. doi: 10.1002/cbin.11979. Epub 2022 Dec 26. PMID: 36571107 Review.
Today, cancer is one of the main health-related challenges, and in the meantime, breast cancer (BC) is one of the most common cancers among women, with an alarming number of incidences and deaths every year. ...After transcription and edition, these two nonco …
Pristimerin Suppressed Breast Cancer Progression via miR-542-5p/DUB3 Axis.
Cheng S, Zhang Z, Hu C, Xing N, Xia Y, Pang B. Onco Targets Ther. 2020 Jul 7;13:6651-6660. doi: 10.2147/OTT.S257329. eCollection 2020. PMID: 32753899 Free PMC article.
BACKGROUND: Breast cancer is one of the most common and malignant tumors in the world. ...MATERIALS AND METHODS: Breast cancer cell lines MCF-7, MDA-MB-231, and 4T1 were used. Cell Counting Kit-8 (CCK-8) assay was performed to evaluate proliferation vi …
miRNA-dependent regulation of STIM1 expression in breast cancer.
Kulkarni RP, Elmi A, Alcantara-Adap E, Hubrack S, Nader N, Yu F, Dib M, Ramachandran V, Najafi Shoushtari H, Machaca K. Sci Rep. 2019 Sep 10;9(1):13076. doi: 10.1038/s41598-019-49629-5. PMID: 31506588 Free PMC article.
Clinically, STIM1 and Ago2 expression levels do not correlate with breast cancer progression, however in the basal subtype high STIM1 expression is associated with poorer survival. Our findings show that STIM1 expression is differentially regulated by the miR …
Inhibitory Effects of Ursolic Acid on the Stemness and Progression of Human Breast Cancer Cells by Modulating Argonaute-2.
Liao WL, Liu YF, Ying TH, Shieh JC, Hung YT, Lee HJ, Shen CY, Cheng CW. Int J Mol Sci. 2022 Dec 26;24(1):366. doi: 10.3390/ijms24010366. PMID: 36613808 Free PMC article.
Furthermore, the co-reduction in oncogenic miRNA levels (miR-9 and miR-221) was a result of the down-modulation in AGO2 in breast cancer cells in vitro. Mechanically, UA increases PTEN expression to inactivate the FAK/PI3K/Akt/mTOR signaling pathway and the d …
Sequestosome 1 (p62) accumulation in breast cancer cells suppresses progesterone receptor expression via argonaute 2.
Yokota A, Hiramoto M, Hino H, Tokuhisa M, Miyazaki M, Kazama H, Takano N, Miyazawa K. Biochem Biophys Res Commun. 2020 Oct 15;531(2):256-263. doi: 10.1016/j.bbrc.2020.07.058. Epub 2020 Aug 13. PMID: 32800344
However, the role of p62 in the breast cancer pathophysiology is still unclear. Here, we aimed to analyze the effect of changes in p62 expression on breast cancer cell lines. ...Moreover, the p62-AGO2-PR axis was identified as a crucial signalin …
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MikroRNA säätelyn merkitys genomissa. Esimerkkinä kalsiumvirtoja säätävät proteiinit ja niiden osuus rintasyöpätyypissä

 kun opittiin tietämään ihmisen genomista DNA, joka säästää  ihmisen proteiinijärjestelmän rakentamiseen tarvittavan tiedon ja   tietoa välittävästä RNA-järjestelmästä,   ei aluksi tiedetty mitä kaikkea tämä  perimän säilytys ja siirto seuraaviin sukupolviin itse asiassa pitää sisällään.  On löydetty yhä pienemåiä  funktiopiirejä ja genemin kantaja ja modulaatioyksiköitä niinettä niisä uutisissa  tuskin moni pysyy edes kärryillä. Kuitenkin ihmiskunta aivan henkensä edestä on tutkimassa tätä koneistoa, koska  vähitellen on havaittu sen häiriöiden olevan  yhä useamman taudin ilmenemän taustalla.  Etsitään keinoja ymmärtää järjestelmää ja sen osasia- niitä näyttää oelvan kuuin tähtiä taivaalla. Voidaan löytöö vaikutuspiirejä kuin tähtikuvioita, orioneita ja otavia ( string) muta jokainen  biokemiallinen kaavakuva sisältää  paljon vaikutuspiirejä jotka eivät ole vielä tiedossa eikä niitä voi merkata kuin   tähtijärjestelmän löytöjä- vasta  menetelmien kehittymisen myötä täydentyy kaikki string- kartat ( proteiini-proteiini-interaktioverkostot) . Tällä kertaa kirjoitan mikroRNA-säätelykoneistosta mutaman rivin ja siten  suomennan yhden artikkelin esimerkkinä. 

On havaittu että ihmisen genomissa on vain osa koodaavaa ainesta ja osa ei-koodaavaa ainesta ( non-coding DNA). Tästä koodaavasta osasta on taas havaittu  jopa mahdollisesti 60% olevan mikroRNA-sääteistä,  Lisäksi tiedemiehet ovat havainneet,että ihmisen genomissa (perintotekijät kantavassa proteiiniaineksessa) esiintyy miltei kaksituhatta mikroRNA-prekursoria, edeltäjämuotoa.  Tämä tieto oli vuodelta 2014. Nyt  varmaan tunnetaan paljon enemmänkin niitä.  MikroRNA-joukko on endogeenisiä pikkuisia yksisäikeisiä RNA-jaksoja, joissa on nukleotidejä 21-24 ja niiden  vaikutus kohdistuu geeniexpression posttransskriptionaaliseen vaiheeseen ( geenin ilmenemän  siihen  vaiheeseen jossa DNA on kirjoittautunut mRNA -muotoon (messenger, lähetti)  , mutta ei vielä käännetty proteiiniksi. Se tapahtuu vasta  translaatiovaiheessa ).MikroRNA  omaa   ydinsekvenssi, mikä on pikkuinen jakso,joka tunnistaa kohde geenin  niiden 3-prim- UTR päädystä ja tämä tunnistus johtaa kohde-mRNA molekyylin ( eli lähettiRNA:n)  silppuroitumiseen  ja/tai sen translaation eli  proteiiniksi kirjoittamisen) estymiseen  (UTR  on jaksoa, jota ei kirjoiteta proteiiniksi ja siihen spesifinen  mikroRNA voi tehdä  oman  merkintänsä)  On niin että mikä tahansa 3prim UTR voi omata  useita sellaisia kohtia, joihin voi  lukuisakin joukko mikroRNA-proteiineja  tehdä jälkensä. Toisaalta mikä tahansa yksittäinen mikroRNA voi vaikuttaa  usean kohteena olevan lähettiRNA:n  3prim-UTR päätyyn .Tämä mekanismi sallii tarkan geenisäätelyn  usealla mikroRNA:lla ja samalla samanaikaissäätelyn  yksittäiselläkin mikroRNA:lla. Varmasti ihmiskunnan tuhansien vuosien  aikana tämä mikroRNA-säätelyn koneisto on konservoinut proteiininsa ja  niitä koodavan järjestelmän, mutta voi kysyä: Entä jos tässä koneistossa on jokin vika, mitä se  vaikuttaa  DNA:lla koodautuvaan ihmiseen. Esim  mikä osuus on  miRNA-säätelykoneiston  vikatoiminnalla ihmisen taudeissa? Tätä selvittellään jatkuvasti. Samoin koetetaan hahmottaa, mitä kaikkea tämä"tähtikuvio " pitää sisällään. Voiko siihen vaikuttaa jotenkin  terveyttä tuottavalla tavalla? Voiko mikroRNA- valmisteilla  saadaa aikaan jotakin  terapeuttista?

Tässä seuraavassa artikkelissa  on selvitelty   kahden erilaisen  metastaattisen rintasyöpäsolukon  mikroRNA-kirjoa ja erästä   kalsiumin aineenvaihduntaan vaikuttavaa  proteiinia STIM1

Tiivistelmää suomeksi :

 Tämä allaolevan  artikkelin työ(Rashmi et al)  työ on tehty  hiirimallissa käyttäen xenokraftia  ja kahta eri tyyppistä rintasyöpäsolukkoa. Toinen solukko merkataan  MCF7, luminaalinen, ei aggressiivisesti kasvava  rintasyöpäsolulinja  ja toinen merkataan MDA-NB-231, aggressiivisesti kasvava basaalinen, trippelnegatiivinen solulinja.  

Tutkijat osoittivat että STIM1 proteiini säätyi mikroRNA-vaikutuksesta. 

Näissä solulinjoissa oli erilainen mikroRNAkirjo.  Ei-aggressiivisessa havaittiin  miR-223 ja miR-150  jotka  säätivät STIM1-proteiinia ( herkkää kalsiumjonin  sensoria), jota esiintyi  matalin pitoisuuksin samoissa soluissa kuin niitä mikro-RNA-lajeja.

 Mutta  aggressiivisesti kasvavassa  solulinjassa  ei STIM-1 säätynyt  mikroRNA-koneistolla  merkitsevästi ja koneistoa näytti  estävän  AGO2  proteiinin alassäätymä. 

Jos AGO2 on ylössäätyneenä  aggressiivisessa solulinjassa  STIM1-proteiinin määrät vähenevät. 

Kliinisesti   STIM1 ja AGO2 eivät kuitenkaan korreloineet  syövän progressioon, mutta aggressiivisessa syövässä    STIM1:n korkea ilmenemä  oli prognostisesti  huono merkki. 

Tutkijoitten päätelmä on, että STIM1 ilmenemä säätyy eri tavalla mikroRNA säätelykoneistosta  rintasyövän eri solutyypeissä  ja mikroRNA säätelyllä  näyttää olevan osuus rintasyövässä.

 OTSIKKO:  MikroRNA.sta riippuva  STIM1-proteiinin ilmenemän säätely rintasyövässä

miRNA-dependent regulation of STIM1 expression in breast cancer

Scientific Reports volume 9, Article number: 13076 (2019) Cite this articleAbstract

Store-operated Ca2+ entry (SOCE) has been shown to be important for breast cancer metastasis in xenograft mouse models. The ER Ca2+ sensor STIM1 and Orai plasma membrane Ca2+ channels molecularly mediate SOCE. Here we investigate the role of the microRNA machinery in regulating STIM1 expression. We show that STIM1 expression is regulated post-transcriptionally by the miRNA machinery and identify miR-223 and miR-150 as regulators of STIM1 expression in the luminal non-aggressive MCF7 breast cancer cell line. In contrast, STIM1 expression in the more aggressive basal triple-negative MDA-MB-231 cell line is not significantly modulated by a single miRNA species but is rather upregulated due to inhibition of the miRNA machinery through downregulation of Ago2. 

Consistently, overexpression of Ago2 results in decreased STIM1 protein levels in MDA-MB-231 cells. 

Clinically, STIM1 and Ago2 expression levels do not correlate with breast cancer progression, however in the basal subtype high STIM1 expression is associated with poorer survival.

 Our findings show that STIM1 expression is differentially regulated by the miRNA machinery in different cell types and argue for a role for this regulation in breast cancer.

 

 Koetan katsoa GeneCards lähteestä teitoa  näistä  termeistä:

 SOCE , Store-operated Calcium ion entry 

Kalsiumjoni on tärkeä solun biologistten toimintojen  säätelytekijänä, siksi sillä on hyvin  laaja joninkäsitely  verkosto. Solun sisällä  kalsiumjonit  kootaan  erilaisiin kalvon ympäröimiin vasrastoihin (store)  ja kalsiumille on  kalvojen läpi johtavia kanavia, joilla on tärkkä säätönsä niin kalsiumin sisäänvirtauksissa kuin ulosvirtauksissa.  Järjestelmä on monijäseninen. 

STIM2  lienee  jotenkin myös  inhibitorinen STIM 1:lle. 

ORAI2 ja STIM2 ovat interaktiossa.

ORAI1, ORAI2 ja ORAI 3 ovat plasmamemraanissa  sijaitsevia kalsiumkanavia.

ORAI1 ja ORAI 3 ovat synergistisiä STIM1 kanssa.

ORAI on interaktiossa   ORAI2, STIM1 ja STIM2  ja usean muun proteiinin kanssa. 

ORAI1  kanssa.  Plays a prominent role in Ca(2+) influx at the basolateral membrane of mammary epithelial cells independently of the Ca(2+) content of endoplasmic reticulum or Golgi stores. May mediate transepithelial transport of large quantities of Ca(2+) for milk secretion.

 

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STIM 1/2 proteiinin interaktioproteiinien laajahko string- kartasto

https://string-db.org/cgi/network?taskId=bfjaCNOALt7n&sessionId=bKHw6sqc7nz2 

https://www.genecards.org/cgi-bin/carddisp.pl?gene=STIM1&keywords=STIM1 

ORAI2: (synergic with STIM1)  https://www.genecards.org/cgi-bin/carddisp.pl?gene=ORAI2&keywords=ORAI2

ORA3 (synergic with STIM1)   https://www.genecards.org/cgi-bin/carddisp.pl?gene=ORAI3&keywords=ORAI3

https://www.genecards.org/cgi-bin/carddisp.pl?gene=STIM2&keywords=STIM2

https://www.genecards.org/cgi-bin/carddisp.pl?gene=ORAI1&keywords=STIM2

ORAI1:   Plays a prominent role in Ca(2+) influx at the basolateral membrane of mammary epithelial cells independently of the Ca(2+) content of endoplasmic reticulum or Golgi stores. May mediate transepithelial transport of large quantities of Ca(2+) for milk secretion. ( CRCM1_HUMAN,Q96D31 )

Edges:
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associations are meant to be specific and meaningful, i.e. proteins jointly contribute to a shared function; this does not necessarily mean they are physically binding to each other.
Known Interactions
from curated databases
experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
gene co-occurrence
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textmining
co-expression
protein homology
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STIM1Stromal interaction molecule 1; Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Acts as Ca(2+) sensor in the endoplasmic reticulum via its EF-hand domain. Upon Ca(2+) depletion, translocates from the endoplasmic reticulum to the plasma membrane where it activates the Ca(2+) release- activated Ca(2+) (CRAC) channel subunit ORAI1. Involved in enamel formation. Activated following interaction with STIMATE, leading to promote STIM1 conformational switch. (791 aa)


ORAI1Calcium release-activated calcium channel protein 1; Ca(2+) release-activated Ca(2+) (CRAC) channel subunit which mediates Ca(2+) influx following depletion of intracellular Ca(2+) stores and channel activation by the Ca(2+) sensor, STIM1. CRAC channels are the main pathway for Ca(2+) influx in T-cells and promote the immune response to pathogens by activating the transcription factor NFAT. Belongs to the Orai family. (301 aa)


STIM2Stromal interaction molecule 2; Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Functions as a highly sensitive Ca(2+) sensor in the endoplasmic reticulum which activates both store-operated and store-independent Ca(2+)-influx. Regulates basal cytosolic and endoplasmic reticulum Ca(2+) concentrations. Upon mild variations of the endoplasmic reticulum Ca(2+) concentration, translocates from the endoplasmic reticulum to the plasma membrane where it probably activates the Ca(2+) release-activated Ca(2+) (CRA [...] (754 aa)


TRPC1Short transient receptor potential channel 1; Thought to form a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G- protein coupled receptors. Seems to be also activated by intracellular calcium store depletion. (793 aa)


ORAI2Protein orai-2; Ca(2+) release-activated Ca(2+)-like (CRAC-like) channel subunit which mediates Ca(2+) influx and increase in Ca(2+)-selective current by synergy with the Ca(2+) sensor, STIM1. (254 aa)


ORAI3Protein orai-3; Key regulator or component of store-operated Ca(2+) channel and transcription factor NFAT nuclear import; Belongs to the Orai family. (295 aa)


MAPRE1Microtubule-associated protein RP/EB family member 1; Plus-end tracking protein (+TIP) that binds to the plus-end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes cytoplasmic microtubule nucleation and elongation. May be involved in spindle function by stabilizing microtubules and anchoring them at centrosomes. Also acts as a regulator of minus-end microtubule organization: interacts with the complex formed by AKAP9 and PDE4DIP, leading to recruit CAMSAP2 to the Golgi apparatus, thereby tethering non-centrosomal minus-end microtubules to the Golgi, a [...] (268 aa)


SARAFStore-operated calcium entry-associated regulatory factor; Negative regulator of store-operated Ca(2+) entry (SOCE) involved in protecting cells from Ca(2+) overfilling. In response to cytosolic Ca(2+) elevation after endoplasmic reticulum Ca(2+) refilling, promotes a slow inactivation of STIM (STIM1 or STIM2)- dependent SOCE activity: possibly act by facilitating the deoligomerization of STIM to efficiently turn off ORAI when the endoplasmic reticulum lumen is filled with the appropriate Ca(2+) levels, and thus preventing the overload of the cell with excessive Ca(2+) ions. (339 aa)


SEC22BVesicle-trafficking protein SEC22b; SNARE involved in targeting and fusion of ER-derived transport vesicles with the Golgi complex as well as Golgi-derived retrograde transport vesicles with the ER. Belongs to the synaptobrevin family. (215 aa)


BAG4BAG family molecular chaperone regulator 4; Inhibits the chaperone activity of HSP70/HSC70 by promoting substrate release (By similarity). Prevents constitutive TNFRSF1A signaling. Negative regulator of PRKN translocation to damaged mitochondria. (457 aa)


SEPTIN11Septin-11; Filament-forming cytoskeletal GTPase. May play a role in cytokinesis (Potential). May play a role in the cytoarchitecture of neurons, including dendritic arborization and dendritic spines, and in GABAergic synaptic connectivity (By similarity). During Listeria monocytogenes infection, not required for the bacterial entry process, but restricts its efficacy. (439 aa)


METTL6tRNA N(3)-methylcytidine methyltransferase METTL6; S-adenosyl-L-methionine-dependent methyltransferase that mediates N(3)-methylcytidine modification of residue 32 of the tRNA anticodon loop of tRNA(Ser); Belongs to the methyltransferase superfamily. METL family. (284 aa)


PDIA3Protein disulfide-isomerase A3; Protein disulfide isomerase family A member 3; Belongs to the protein disulfide isomerase family. (505 aa)


SEC63Translocation protein SEC63 homolog; Mediates cotranslational and post-translational transport of certain precursor polypeptides across endoplasmic reticulum (ER). Proposed to play an auxiliary role in recognition of precursors with short and apolar signal peptides. May cooperate with SEC62 and HSPA5/BiP to facilitate targeting of small presecretory proteins into the SEC61 channel-forming translocon complex, triggering channel opening for polypeptide translocation to the ER lumen. Required for efficient PKD1/Polycystin- 1 biogenesis and trafficking to the plasma membrane of the primary [...] (760 aa)


JUNTranscription factor AP-1; Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'. Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. Involved in activated KRAS-mediated transcriptional activation of USP28 in colorectal cancer (CRC) cells. Binds to the USP28 promoter in colorectal cancer (CRC) cells. Belongs to the bZIP family. Jun subfamily. (331 aa)


STX18Syntaxin-18; Syntaxin that may be involved in targeting and fusion of Golgi-derived retrograde transport vesicles with the ER. (335 aa)


HSP90B1Endoplasmin; Molecular chaperone that functions in the processing and transport of secreted proteins (By similarity). When associated with CNPY3, required for proper folding of Toll-like receptors (By similarity). Functions in endoplasmic reticulum associated degradation (ERAD). Has ATPase activity (By similarity). Belongs to the heat shock protein 90 family. (803 aa)


UBE2J1Ubiquitin-conjugating enzyme E2 J1; Catalyzes the covalent attachment of ubiquitin to other proteins. Functions in the selective degradation of misfolded membrane proteins from the endoplasmic reticulum (ERAD). Belongs to the ubiquitin-conjugating enzyme family. (318 aa)


CANXCalnexin; Calcium-binding protein that interacts with newly synthesized glycoproteins in the endoplasmic reticulum. It may act in assisting protein assembly and/or in the retention within the ER of unassembled protein subunits. It seems to play a major role in the quality control apparatus of the ER by the retention of incorrectly folded proteins. Associated with partial T-cell antigen receptor complexes that escape the ER of immature thymocytes, it may function as a signaling complex regulating thymocyte maturation. Additionally it may play a role in receptor-mediated endocytosis at t [...] (592 aa)


HEXBBeta-hexosaminidase subunit beta chain A; Responsible for the degradation of GM2 gangliosides, and a variety of other molecules containing terminal N-acetyl hexosamines, in the brain and other tissues; Belongs to the glycosyl hydrolase 20 family. (556 aa)


ATP2B4Plasma membrane calcium-transporting ATPase 4; Calcium/calmodulin-regulated and magnesium-dependent enzyme that catalyzes the hydrolysis of ATP coupled with the transport of calcium out of the cell. By regulating sperm cell calcium homeostasis, may play a role in sperm motility (By similarity). Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIB subfamily. (1205 aa)


RELATranscription factor p65; NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain- containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The heterodimeric RELA-NFKB1 complex appears to be most abundant one. The dimers bind at kap [...] (551 aa)


HSCBIron-sulfur cluster co-chaperone protein HscB, mitochondrial; Acts as a co-chaperone in iron-sulfur cluster assembly in both mitochondria and the cytoplasm. Required for incorporation of iron-sulfur clusters into SDHB, the iron- sulfur protein subunit of succinate dehydrogenase that is involved in complex II of the mitochondrial electron transport chain. Recruited to SDHB by interaction with SDHAF1 which first binds SDHB and then recruits the iron-sulfur transfer complex formed by HSC20, HSPA9 and ISCU through direct binding to HSC20. Also mediates complex formation between components [...] (235 aa)


LMBR1LProtein LMBR1L; Plays an essential role in lymphocyte development by negatively regulating the canonical Wnt signaling pathway (By similarity). In association with UBAC2 and E3 ubiquitin-protein ligase AMFR, promotes the ubiquitin-mediated degradation of CTNNB1 and Wnt receptors FZD6 and LRP6 (By similarity). LMBR1L stabilizes the beta- catenin destruction complex that is required for regulating CTNNB1 levels (By similarity). Acts as a LCN1 receptor and can mediate its endocytosis. Belongs to the LIMR family. (489 aa)


EFHBEF-hand domain-containing family member B; Cytosolic sensor for calcium, modulates the interaction of STIM1 and ORAI1 upon store depletion, the activation of store-operated Ca(2+) entry (SOCE) and NFAT translocation from cytosol to nucleus. (833 aa)


FOSProto-oncogene c-Fos; Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. In the heterodimer, FOS and JUN/AP-1 basic regions each seems to interact with symmetrical DNA half sites. On TGF-beta activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex at the AP1/SMAD-binding site to regulate TGF-beta-mediated signaling. Has a critical function in regulating the development of cells destined to form and maintain the skeleton. It is thought to have an important role in signal transduction, cell proliferation and differentia [...] (380 aa)
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Pub Med haku: miRNA regulation machinery in Breast Cancer? (61 results)

 

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61 results
miRNA-dependent regulation of STIM1 expression in breast cancer.
Kulkarni RP, Elmi A, Alcantara-Adap E, Hubrack S, Nader N, Yu F, Dib M, Ramachandran V, Najafi Shoushtari H, Machaca K. Sci Rep. 2019 Sep 10;9(1):13076. doi: 10.1038/s41598-019-49629-5. PMID: 31506588 Free PMC article.
Here we investigate the role of the microRNA machinery in regulating STIM1 expression. We show that STIM1 expression is regulated post-transcriptionally by the miRNA machinery and identify miR-223 and miR-150 as regulators of STIM1 expres …
Role of tRNAs in Breast Cancer Regulation.
Kwon NH, Lee JY, Kim S. Adv Exp Med Biol. 2021;1187:121-145. doi: 10.1007/978-981-32-9620-6_6. PMID: 33983576 Review.
With the development of high throughput technologies such as next-generation sequencing, genome-wide differential tRNA expression patterns in breast cancer-derived cell lines and breast tumors have been investigated. The genome-wide transcriptomics analyses h …
MicroRNAs in Breast Cancer: One More Turn in Regulation.
Eroles P, Tormo E, Pineda B, Espin E, Lluch A. Curr Drug Targets. 2016;17(9):1083-100. doi: 10.2174/1389450116666150213114103. PMID: 25694121 Review.
This review provides an overview of the current situation of miRNAs in breast cancer, focusing on their involvement in resistance and the circulating miRNA. The mechanisms of therapeutic resistance regulated by miRNAs, such as the regu …
Dissecting miRNA facilitated physiology and function in human breast cancer for therapeutic intervention.
Sengupta D, Deb M, Kar S, Pradhan N, Parbin S, Kirtana R, Singh SP, Suma SG, Niharika, Roy A, Manna S, Saha P, Chakraborty P, Dash S, Kausar C, Patra SK. Semin Cancer Biol. 2021 Jul;72:46-64. doi: 10.1016/j.semcancer.2020.05.017. Epub 2020 Jun 1. PMID: 32497683 Review.
MicroRNAs (miRNAs) are key epigenomic regulators of biological processes in animals and plants. ...Aberrant regulation of gene expression by miRNAs is frequently observed in cancer. ...
Epigenetic Regulation of microRNAs in Cancer: Shortening the Distance from Bench to Bedside.
Pajares MJ, Alemany-Cosme E, Goñi S, Bandres E, Palanca-Ballester C, Sandoval J. Int J Mol Sci. 2021 Jul 8;22(14):7350. doi: 10.3390/ijms22147350. PMID: 34298969 Free PMC article. Review.
In this sense, aberrant miRNA landscape evaluation has emerged as a promising strategy for cancer management. In this review, we have focused on the regulation (biogenesis, processing, and dysregulation) of miRNAs and their role as modulators of the ep …
Role of the Mediator Complex and MicroRNAs in Breast Cancer Etiology.
Maldonado E, Morales-Pison S, Urbina F, Jara L, Solari A. Genes (Basel). 2022 Jan 26;13(2):234. doi: 10.3390/genes13020234. PMID: 35205279 Free PMC article. Review.
MED transduces the signal between DNA-bound transcriptional activators (gene-specific transcription factors) to the RNA polymerase II transcription machinery to activate transcription. It is known that MED plays an essential role in ER-mediated gene expression mainly throu …
Recent Advances in Comprehending the Signaling Pathways Involved in the Progression of Breast Cancer.
Nicolini A, Ferrari P, Diodati L, Carpi A. Int J Mol Sci. 2017 Nov 3;18(11):2321. doi: 10.3390/ijms18112321. PMID: 29099748 Free PMC article. Review.
This review describes recent advances in the comprehension of signaling pathways involved in breast cancer progression. Calcium sensing receptor (CaSR), caveolae signaling, signaling referred to hypoxia-inducing factors and disturbances in the apoptotic machinery …
KLK6-regulated miRNA networks activate oncogenic pathways in breast cancer subtypes.
Sidiropoulos KG, Ding Q, Pampalakis G, White NM, Boulos P, Sotiropoulou G, Yousef GM. Mol Oncol. 2016 Aug;10(7):993-1007. doi: 10.1016/j.molonc.2016.03.008. Epub 2016 Apr 8. PMID: 27093921 Free PMC article.
KLK6 is expressed in normal mammary tissues and is aberrantly regulated in breast cancer. At physiological levels of expression, i.e. those found in normal mammary tissues, KLK6 acts as a tumor suppressor in human breast cancer. ...Cancer …
Epigenetic regulation of miR-200 as the potential strategy for the therapy against triple-negative breast cancer.
Mekala JR, Naushad SM, Ponnusamy L, Arivazhagan G, Sakthiprasad V, Pal-Bhadra M. Gene. 2018 Jan 30;641:248-258. doi: 10.1016/j.gene.2017.10.018. Epub 2017 Oct 14. PMID: 29038000 Review.
MicroRNAs (miRNAs) are a class of small, non-coding RNAs that are involved in the regulation of gene expression at the post-transcriptional level. ...We also discuss the need for identifying novel HDAC inhibitors for modulation of miR-200 in triple negative …
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tisdag 5 mars 2024

S100B merkkiaineena syövässä

 https://pubmed.ncbi.nlm.nih.gov/29345293/

. Our results revealed that a high S100B expression predicted a good overall survival in patients with ER-negative breast cancer, and good distant metastases-free survival in all patients with breast cancer via the analysis of the KM plotter and SurvExpress databases. Although previous studies have indicated that the interaction of S100B with wild-type p53 inhibits p53 function, a high S100B expression is associated with a good prognosis in patients with p53 mutant and p53 wild-type breast cancers. On the whole, our findings demonstrate that S100B treatment suppresses the migratory capacity of ER-negative breast cancer and that S100B expression may serve a predictive marker for metastasis in breast cancer. 

 

S100B and S100B autoantibody as biomarkers for early detection of brain metastases in lung cancer.

Choi H, Puvenna V, Brennan C, Mahmoud S, Wang XF, Phillips M, Janigro D, Mazzone P. Transl Lung Cancer Res. 2016 Aug;5(4):413-9. doi: 10.21037/tlcr.2016.07.08. PMID: 27652205 Free PMC article.
We explored the use of serum S100B protein and S100B autoantibodies for the detection of brain metastasis in patients with lung cancer. ...CONCLUSIONS: Serum S100B and S100B autoantibody levels may help to identify which lung cancer patie …

 

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