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miR-378a-3p 通过靶向 Rab10 对食管鳞状细胞癌的发生发挥肿瘤抑制作用。

miR‑378a‑3p exerts tumor suppressive function on the tumorigenesis of esophageal squamous cell carcinoma by targeting Rab10.

机构信息

Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210009, P.R. China.

出版信息

Int J Mol Med. 2018 Jul;42(1):381-391. doi: 10.3892/ijmm.2018.3639. Epub 2018 Apr 24.

Abstract

Esophageal squamous cell carcinoma (ESCC) is a life‑threatening cancer with increasing incidence worldwide. MicroRNAs (miRs) have been reported to be involved in the progression of various types of cancer. In previous studies, the expression of miR‑378a‑3p was shown to be reduced in ESCC tissues. However, the mechanism underlying the effect of miR‑378a‑3p in ESCC remains to be elucidated. By employing a reverse transcription‑quantitative polymerase chain reaction, miR‑378a‑3p expression was tested in ESCC tissues and cell lines. In addition, the effects of miR‑378a‑3p on cell viability, proliferation, apoptosis, migration and invasion were studied using an MTT assay, an EdU assay, flow cytometry analysis, wound healing analysis and a Transwell assay. In the present study, the level of miR‑378a‑3p was significantly downregulated in ESCC clinical tissues and cell lines (EC109 and KYSE150). In addition, the overexpression of miR‑378a‑3p suppressed the viability, proliferation, migration and invasion of the ESCC cells. The upregulated expression of miR‑378a‑3p also increased the expression levels of B‑cell lymphoma 2‑associated X protein and caspase‑3, and decreased the expression levels of matrix metalloproteinase (MMP)‑2 and MMP‑9, which attenuated ESCC tumorigenesis. Furthermore, Rab10 was confirmed to be a direct target gene of miR‑378a‑3p, and was negatively affected by miR‑378a‑3p. The silencing of Rab10 revealed antitumor effects in ESCC cell lines, and the expression of miR‑378a‑3p was negatively correlated with that of Rab10 in ESCC. Collectively, miR‑378a‑3p may act as a tumor‑suppressor in ESCC cells through negatively regulating Rab10.

摘要

食管鳞状细胞癌 (ESCC) 是一种危及生命的癌症,其发病率在全球范围内呈上升趋势。研究表明,微小 RNA (miRs) 参与了多种类型癌症的进展。在之前的研究中,miR-378a-3p 在 ESCC 组织中的表达降低。然而,miR-378a-3p 在 ESCC 中的作用机制仍有待阐明。通过逆转录-定量聚合酶链反应检测 ESCC 组织和细胞系中 miR-378a-3p 的表达。此外,通过 MTT 检测、EdU 检测、流式细胞术分析、划痕愈合分析和 Transwell 检测研究 miR-378a-3p 对细胞活力、增殖、凋亡、迁移和侵袭的影响。在本研究中,miR-378a-3p 的水平在 ESCC 临床组织和细胞系(EC109 和 KYSE150)中显著下调。此外,miR-378a-3p 的过表达抑制了 ESCC 细胞的活力、增殖、迁移和侵袭。miR-378a-3p 的上调表达还增加了 B 细胞淋巴瘤 2 相关 X 蛋白和半胱天冬酶-3 的表达水平,降低了基质金属蛋白酶 (MMP)-2 和 MMP-9 的表达水平,从而减弱了 ESCC 的肿瘤发生。此外,Rab10 被证实是 miR-378a-3p 的直接靶基因,并且受 miR-378a-3p 的负调控。Rab10 的沉默在 ESCC 细胞系中显示出抗肿瘤作用,并且 miR-378a-3p 在 ESCC 中的表达与 Rab10 的表达呈负相关。总之,miR-378a-3p 可能通过负调控 Rab10 在 ESCC 细胞中发挥肿瘤抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3060/5979826/f75ec0d9e80a/IJMM-42-01-0381-g00.jpg

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