Oncotarget. 2016 Dec 27;7(52):86755-86765. doi: 10.18632/oncotarget.13550.
TRIM11, a direct target of miR-24-3p, promotes cell proliferation and inhibits apoptosis in colon cancer.
Abstract
TRIM11
(tripartite motif-containing protein 11) is an E3 ubiquitin ligase
recently identified as an oncogene in malignant glioma and lung cancer.
In the present study, we report that expression of TRIM11 was increased
in colon cancer (CC) tissue relative to paired normal tissues and that
higher TRIM11 levels predicted poor overall survival (OS) and
disease-free survival (DFS) in CC patients. Mechanistically, we showed
that miR-24-3p downregulation contributes to TRIM11 upregulation in CC.
We also demonstrated that TRIM11 overexpression promotes cell
proliferation and colony formation and inhibits apoptosis in CC, while
knocking down TRIM11 using CRISPR/Cas9-mediated genome editing inhibited
cell proliferation and induced apoptosis. Silencing TRIM11 in vivo
decreased tumor growth. These findings indicate that TRIM11 facilitates
CC progression by promoting cell proliferation and inhibiting apoptosis
and that the novel miR-24-3p/TRIM11 axis may be a useful new target for
treating patients with CC. KEYWORDS: TRIM11; colon cancer; miR-24-3p
Lisätietoa miR-24-3p mikroRNA:sta
miR-34-30 osallistuu syöpään liittyviin soluprosesseihin, kuten solusyklin kontrolliin, solun kasvuun, proliferaatioon ja apoptoosiin-
https://www.sciencedirect.com/science/article/pii/S0009912016303873
Elevated expression of miR-24-3p is a potentially adverse prognostic factor in colorectal adenocarcinoma
https://doi.org/10.1016/j.clinbiochem.2016.11.034Get
Abstract Objectives
Several miRNAs are aberrantly expressed in cancer. miR-24-3p is involved in cancer-related cellular processes, including
cell cycle control,
cell growth, proliferation, and
apoptosis.
In this study, we examined the potential diagnostic and prognostic
significance of miR-24-3p expression in colorectal adenocarcinoma.
Design and methods
Total RNA was isolated from 182 colorectal adenocarcinoma specimens and 86 paired non-cancerous colorectal
mucosae. After
polyadenylation of 2 μg total RNA and
reverse transcription into first-strand cDNA using an oligo-dT-adapter
primer, miR-24-3p expression was quantified using an in-house–developed reverse-transcription real-time
quantitative PCR method, based on the
SYBR Green chemistry.
SNORD43 (
RNU43) was used as a reference gene.
Results
miR-24-3p
levels do not significantly differ between colorectal adenocarcinoma
and non-cancerous colorectal mucosae. Thus, miR-24-3p expression cannot
be used for diagnostic purposes. However, high miR-24-3p expression
predicts poor disease-free survival (DFS) and overall survival (OS) of
colorectal adenocarcinoma patients. Multivariate Cox regression analysis
confirmed that miR-24-3p overexpression is a significant predictor of
relapse in colorectal adenocarcinoma and that its prognostic
significance is independent of other established
prognostic factors
and treatment of patients. Of note, miR-24-3p overexpression retains
its rather unfavorable prognostic value in the subgroup of patients with
advanced yet locally restricted colorectal adenocarcinoma (T3) and in
those without distant metastasis (M0). Moreover, miR-24-3p
overexpression is a potentially unfavorable prognosticator for patients
who were not treated with
radiotherapy.
Conclusions
Strong
expression of miR-24-3p predicts poor DFS and OS of colorectal
adenocarcinoma patients, independently of clinicopathological parameters
that are currently used for prognosis in this human malignancy.
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