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MicroRNA?212 facilitates the motility and invasiveness of esophageal squamous carcinoma cells.

ABSTRACT: As a tumor?associated microRNA (miR), miR?212 has dual functions; either as an oncogene or a tumor suppressor. A high expression level of miR?212 was reported to be associated with poor outcome in patients with esophageal squamous cell carcinoma (ESCC), however, its role in ESCC progression has not been explored. In the present study, an in vitro cell model of lentivirus?mediated gain?of?function demonstrated promotion of ESCC cell migration and invasion when miR?212 was overexpressed, and no effect on cell proliferation. miR?212 resulted in downregulation of the expression of E?cadherin, ??catenin, vimentin and Twist1. Moreover, it led to increased levels of extracellular matrix (ECM)?degrading enzymes, matrix metalloproteinase?9 and urokinase?type plasminogen activator. Furthermore, berberine inhibited miR?212?induced ESCC cell migration, unlike the PI3K inhibitor LY294002, rapamycin (mTOR inhibitor), 5?(Tetradecyloxy)?2?furoic acid (TOFA; an acetyl?CoA carboxylase 1 inhibitor), metformin and propranolol. These data suggest that miR?212 activates multiple signaling cascades and facilitates ESCC cell motility and invasion by promoting the epithelial?mesenchymal transition and degrading the ECM. Berberine may be a potential therapeutic agent against metastasis in patients with ESCC, who express high levels of miR?212.

SUBMITTER: Chen Z

PROVIDER: S-EPMC6755231 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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MicroRNA‑212 facilitates the motility and invasiveness of esophageal squamous carcinoma cells.

Chen Zhi Z Liu Yuzhen Y Qi Bo B Gu Chengwei C Wei Xiufeng X Guo Ling L Yao Wenjian W Zhao Baosheng B

Molecular medicine reports 20190903 4

As a tumor‑associated microRNA (miR), miR‑212 has dual functions; either as an oncogene or a tumor suppressor. A high expression level of miR‑212 was reported to be associated with poor outcome in patients with esophageal squamous cell carcinoma (ESCC), however, its role in ESCC progression has not been explored. In the present study, an in vitro cell model of lentivirus‑mediated gain‑of‑function demonstrated promotion of ESCC cell migration and invasion when miR‑212 was overexpressed, and no ef ...[more]

PMID: 31485658

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Project description:Background and aimsMicroRNAs including miR146a have a regulatory role on the expression of genes and act with binding to 3'-UTR region of the genes. Cyclooxygenase-2 (COX-2) is involved in carcinogenesis as an inflammatory marker, and microRNA-146a (miR-146a) as a negative regulatory factor. We aimed to evaluate miR146a expression as a prognostic or diagnostic biomarker for esophageal squamous cell carcinoma (ESCC) and also an association between miR146a and COX2 expression.Materials and methodsWe quantified the level of miR-146a and COX-2 expression in cancerous and adjacent normal tissue samples obtained from 34 patients with ESCC, using real-time-PCR. Statistical analyses were conducted using one-sample t-test. Receiver-operating characteristic (ROC) curve and Kaplan-Meier analysis were applied to assay miR146a as a diagnostic and prognostic marker, respectively, during 4 years of the study. Furthermore, the Cox regression model was performed to assay the hazard ratio (HR). The association between miR-146a and COX2 expression level in ESCC patients was evaluated by nonparametric Spearman's rho analysis.ResultsThe results revealed a reduction of miR-146a expression in 50% of cancerous tissue when compared with adjacent normal regions (P-value=0.127). COX-2 expression in 80% of ESCC patients was higher than in the controls (P-value=0.001). Overall, in 60% of cases, direct association was seen between microRNA-146a and COX-2 expression level (correlation coefficient= 0.438, P-value=0.011). COX2 can be considered as a diagnostic biomarker (AUC=0.834, sensitivity=72%, specificity =83%, P-value<0.0001) but miR146a cannot be considered as a diagnostic biomarker (AUC=0.553, sensitivity=88%, specificity =28%, P-value=0.453). Survival analysis by Kaplan-Meier method showed miR146a and COX2 expression can be probably considered as prognostic biomarkers for ESCC because patients with high expression of miR146a had 7 months shorter life span and patients with low expression of COX2 had 8 months shorter life span.ConclusionCOX2 expression is a diagnostic biomarker. MiR-146a and COX2 expression can probably be considered as prognostic biomarkers for survival in ESCC.

Project description:BACKGROUND:MicroRNA (miR)s are promising diagnostic biomarkers of cancer. Recent next generation sequencer (NGS) studies have found that isoforms of micro RNA (isomiR) circulate in the bloodstream similarly to mature micro RNA (miR). We hypothesized that combination of circulating miR and isomiRs detected by NGS are potentially powerful cancer biomarker. The present study aimed to investigate their application in esophageal cancer. METHODS:Serum samples from patients with esophageal squamous cell carcinoma (ESCC) and age and sex matched healthy control (HC) individuals were investigated for the expression of miR/isomiRs using NGS. Candidate miR/isomiRs which met the criteria in the 1st group (ESCC = 18 and HC = 12) were validated in the 2nd group (ESCC = 30 and HC = 30). A diagnostic panel was generated using miR/isomiRs that were consistently confirmed in the 1st and 2nd groups. Accuracy of the panel was tested then in the 3rd group (ESCC = 18 and HC = 18). Their use was also investigated in 22 paired samples obtained pre- and post-treatment, and in patients with esophageal adenocarcinoma (EAD) and high-grade dysplasia (HGD). RESULTS:Twenty-four miR/isomiRs met the criteria for diagnostic biomarker in the 1st and 2nd group. A multiple regression model selected one mature miR (miR-30a-5p) and two isomiRs (isoform of miR-574-3p and miR-205-5p). The index calculated from the diagnostic panel was significantly higher in ESCC patients than in the HCs (13.3±8.9 vs. 3.1±1.3, p<0.001). The area under the receiver operating characteristics (ROC) curves of the panel index was 0.95. Sensitivity and specificity were 93.8%, and 81% in the 1st and 2nd groups, and 88.9% and 72.3% in the 3rd group, respectively. The panel index was significantly lower in patients with EAD (6.2±4.5) and HGD (4.2±1.7) than in those with ESCC and was significantly decreased at post-treatment compared with pre-treatment (6.2±5.6 vs 11.6±11.5, p = 0.03). CONCLUSION:Our diagnostic panel had high accuracy in the diagnosis of ESCC. MiR/isomiRs detected by NGS could serve as novel biomarkers of ESCC.

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MicroRNA?212 facilitates the motility and invasiveness of esophageal squamous carcinoma cells.

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MicroRNA‑212 facilitates the motility and invasiveness of esophageal squamous carcinoma cells.

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