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MiR?144?3p inhibits tumor cell growth and invasion in oral squamous cell carcinoma through the downregulation of the oncogenic gene, EZH2.

ABSTRACT: Accumulating evidence demonstrates that microRNAs (miRNAs or miRs) play important roles in the development and progression of human malignancies, including oral squamous cell carcinoma (OSCC); however, the unique roles of miRNAs are not yet fully understood in OSCC. The present study aimed to identify novel miRNAs associated with OSCC and to elucidate their functions. Based on a microarray analysis, miR?144?3p was found to be one of the most significantly downregulated miRNAs in OSCC tissues. Its low expression was closely associated with tumor size, differentiation and lymph node metastasis. Functionally, miR?144?3p overexpression suppressed proliferation, promoted apoptosis, and suppressed the invasion and migration of OSCC cells. In addition, enhancer of zeste homolog 2 (EZH2), a well?known oncogene, was proven to be a direct target of miR?144?3p, and its protein expression was negatively regulated by miR?144?3p. Moreover, EZH2 expression was increased, and inversely correlated with the miR?144?3p level in OSCC tissues. Notably, EZH2 knockdown inhibited cell proliferation, promoted cell apoptosis, and suppressed the invasion and migration of OSCC cells, whereas EZH2 overexpression partially reversed the anticancer effects mediated by miR?144?3p overexpression. On the whole, the findings of the present study suggest that miR?144?3p functions as a tumor suppressor by targeting the EZH2 oncogene, and may thus be considered as a potential diagnostic and therapeutic target for OSCC.

SUBMITTER: He L

PROVIDER: S-EPMC7307824 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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miR‑144‑3p inhibits tumor cell growth and invasion in oral squamous cell carcinoma through the downregulation of the oncogenic gene, EZH2.

He Longlong L Liao Lifan L Du Liangzhi L

International journal of molecular medicine 20200611 2

Accumulating evidence demonstrates that microRNAs (miRNAs or miRs) play important roles in the development and progression of human malignancies, including oral squamous cell carcinoma (OSCC); however, the unique roles of miRNAs are not yet fully understood in OSCC. The present study aimed to identify novel miRNAs associated with OSCC and to elucidate their functions. Based on a microarray analysis, miR‑144‑3p was found to be one of the most significantly downregulated miRNAs in OSCC tissues. It ...[more]

PMID: 32626925

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Project description:BackgroundMicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression, influence cellular processes, and promote disease development. Variations in miRNA expression have been observed in many diseases, including hepatitis, cardiovascular disease, and cancer. The aim of this study is to investigate the effect of miR-144-3p on the invasion and metastasis of lung adenocarcinoma by targeting recombinant insulin receptor substrate 1 (IRS1).MethodsThe expression of miR-144-3p in patients with lung adenocarcinoma was queried through bioinformatics database. MirTarPathway was used to analyze the KEGG enrichment pathway of miRNA. The expression and plasmid transfection efficiency of miR-144-3p in lung adenocarcinoma cell lines were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Transwell assay was used to detect the changes of cell invasion and migration ability in different groups. Bioinformatics determined the key genes (Hub genes) of miR-144-3p; Double luciferase target assay was used to detect the mutual binding of miR-144 and IRS1. Western blot assay was used to detect the expression of IRS1 in different cell lines and the expression of after overexpression of miR-144.ResultsThe expression of miR-144-3p in lung adenocarcinoma tissues was decreased, qRT-PCR results indicated that the expression of miR-144-3p in lung adenocarcinoma cell A549 was significantly decreased (P<0.05), and the overexpressed plasmid was successfully transfected (P<0.05). Overexpression of miR-144 decreased the ability of cell migration and invasion (P<0.05). The expression of IRS1 was up-regulated in lung adenocarcinoma tissues. Survival analysis showed that patients with lung adenocarcinoma with high IRS1 expression had a poor prognosis (P<0.05). Double luciferase assay results showed that miR-144 could specifically identify 3'-UTR of IRS1 and inhibit reporter enzyme expression (P<0.05). Western blot indicated that the expression of IRS1 was increased in A549 cells (P<0.05). After overexpression of miR-144, the expression level of IRS1 protein was decreased (P<0.05). Transwell experiment proved that miR-144-3p could inhibit invasion and metastasis of lung adenocarcinoma cells by targeting IRS1 (P<0.05).ConclusionsMiR-144-3p inhibits the invasion and migration of A549 cells through targeted regulation of IRS1, thus playing an anticancer role in tumors.

Dataset Information

MiR?144?3p inhibits tumor cell growth and invasion in oral squamous cell carcinoma through the downregulation of the oncogenic gene, EZH2.

Publications

miR‑144‑3p inhibits tumor cell growth and invasion in oral squamous cell carcinoma through the downregulation of the oncogenic gene, EZH2.

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