Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China.
Oncol Rep. 2017 Dec;38(6):3465-3472. doi: 10.3892/or.2017.6020. Epub 2017 Oct 10.
Gastric cancer (GC) is one of the most common malignant diseases worldwide. Although significant progress has been made in the early detection and treatment of GC over the past decades, the prognosis is still not satisfactory and the underlying mechanisms of carcinogenesis remain unknown. Long non-coding RNA MIAT has been established as a key player in the regulation of various biological and pathological processes including chronic lymphocytic leukemias, acute myocardial infarction and neuroendocrine prostate cancer. However, the function of MIAT in GC remains largely unknown. The expressions of lncRNA MIAT, miR-29a-3p and HDAC4 mRNA were analysed using quantitative real-time PCR (qRT-PCR). RNA interference approach was used to investigate the cellular functions of MIAT and miR-29a-3p. Cell Counting Kit-8 (CCK-8) assay and flow cytometry assay were performed to detect cell proliferation and apoptosis. Cell migration and invasion abilities were evaluated by Transwell assays. In the present study, we first confirmed the high expression level of MIAT in GC tissues and cell lines. In addition, knockdown of MIAT suppressed the proliferation, migration and invasion of GC cells in vitro. Furthermore, our results demonstrated that MIAT competitively binds to miR-29a-3p and consequently upregulates the expression of HDAC4, which is a downstream target of miR-29a-3p. In conclusion, the present study highlighted the involvement of the MIAT/miR-29a-3p/HDAC4 axis in the development of GC, which provided potential diagnostic and therapeutic targets for GC.
胃癌(GC)是全球最常见的恶性疾病之一。尽管在过去几十年中,GC 的早期检测和治疗取得了重大进展,但预后仍然不尽如人意,其致癌机制仍不清楚。长链非编码 RNA MIAT 已被确定为调节包括慢性淋巴细胞白血病、急性心肌梗死和神经内分泌前列腺癌在内的各种生物学和病理过程的关键因素。然而,MIAT 在 GC 中的功能仍然知之甚少。采用实时定量 PCR(qRT-PCR)分析 lncRNA MIAT、miR-29a-3p 和 HDAC4 mRNA 的表达。采用 RNA 干扰方法研究 MIAT 和 miR-29a-3p 的细胞功能。通过细胞计数试剂盒-8(CCK-8)测定和流式细胞术检测细胞增殖和凋亡。通过 Transwell 测定评估细胞迁移和侵袭能力。在本研究中,我们首先证实了 MIAT 在 GC 组织和细胞系中的高表达水平。此外,MIAT 的敲低抑制了 GC 细胞在体外的增殖、迁移和侵袭。此外,我们的结果表明,MIAT 竞争性结合 miR-29a-3p,从而上调 HDAC4 的表达,HDAC4 是 miR-29a-3p 的下游靶标。总之,本研究强调了 MIAT/miR-29a-3p/HDAC4 轴在 GC 发展中的作用,为 GC 提供了潜在的诊断和治疗靶点。