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微小 RNA-302a 通过直接靶向 VEGFA 抑制肝癌细胞增殖、侵袭,诱导细胞凋亡。

MicroRNA‑302a inhibits cell proliferation and invasion, and induces cell apoptosis in hepatocellular carcinoma by directly targeting VEGFA.

机构信息

Department of General Surgery, The Fourth Affiliated Hospital of Nantong Medical College, Yancheng City No. 1 People's Hospital, Yancheng, Jiangsu 224001, P.R. China.

出版信息

Mol Med Rep. 2017 Nov;16(5):6360-6367. doi: 10.3892/mmr.2017.7312. Epub 2017 Aug 22.

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer‑related mortality worldwide. An increasing number of studies have demonstrated that microRNAs may be used as diagnostic, therapeutic and prognostic targets for human cancers, including HCC. The present study aimed to evaluate microRNA (miR)‑302a expression and function in HCC, and its underlying mechanisms. The results revealed that miR‑302a was expressed at low levels in HCC tissues and cell lines. Reduced miR‑302a expression was correlated with tumor‑node‑metastasis stage and lymph node metastasis in patients with HCC. Additionally, overexpression of miR‑302a reduced cell proliferation and invasion, and induced apoptosis in HCC cells. Vascular endothelial growth factor A (VEGFA) was demonstrated to be a direct target gene of miR‑302a. VEGFA was highly expressed in HCC tissues and inversely correlated with miR‑302a expression. Knockdown of VEGFA expression led to reduced HCC cell proliferation and invasion, and increased apoptosis rates, similar to miR‑302a overexpression, which suggested that VEGFA may be a functional downstream target of miR‑302a in HCC. These data suggested that this newly identified miR‑302a/VEGFA axis may be involved in HCC formation and progression. The present results also provide novel potential targets for the treatments of patients with HCC.

摘要

肝细胞癌 (HCC) 是全球第五大常见癌症,也是癌症相关死亡的第三大主要原因。越来越多的研究表明,微小 RNA (miRNA) 可作为人类癌症,包括 HCC 的诊断、治疗和预后靶点。本研究旨在评估 miRNA (miR) -302a 在 HCC 中的表达和功能及其潜在机制。结果显示,miR-302a 在 HCC 组织和细胞系中的表达水平较低。miR-302a 表达降低与 HCC 患者的肿瘤-淋巴结-转移分期和淋巴结转移相关。此外,miR-302a 的过表达降低了 HCC 细胞的增殖和侵袭能力,并诱导其凋亡。血管内皮生长因子 A (VEGFA) 被证实是 miR-302a 的直接靶基因。VEGFA 在 HCC 组织中高表达,与 miR-302a 的表达呈负相关。VEGFA 表达的敲低导致 HCC 细胞增殖和侵袭减少,凋亡率增加,与 miR-302a 的过表达相似,这表明 VEGFA 可能是 HCC 中 miR-302a 的功能性下游靶基因。这些数据表明,新鉴定的 miR-302a/VEGFA 轴可能参与 HCC 的形成和进展。本研究结果还为 HCC 患者的治疗提供了新的潜在靶点。

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