Xu X-C, Zhang Y-H, Zhang W-B, Li T, Gao H, Wang Y-H
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China.
Department of Pathology, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China.
J Biol Regul Homeost Agents. 2014 Oct-Dec;28(4):615-24.
MicroRNAs (miRNAs) are small and highly conserved non-coding RNAs that regulate gene expression of target mRNAs through posttranscriptional inhibition involved in the tumorigenesis and progression of multiple malignancies. Although miR-133a has been shown to function as a tumor suppressor in some cancers, the clinical significance and function of miR-133a in gastric cancer remain unclear. Hence, we were focused on the expression and mechanisms of miR-133a in the development of gastric cancer in this study. It was found that the expression of miR-133a was downregulated (P<0.001), while transgelin-2 (TAGLN2) was upregulated (P<0.05) in primary gastric cancer tissues, compared to the adjacent non-cancerous tissues (ANCT). Furthermore, decreased expression of miR-133a and increased expression of TAGLN2 were both associated with lymph node metastases in patients with gastric cancer (P<0.001; P=0.011). Functional analysis studies revealed that ectopic expression of miR-133a reduced cell proliferation and invasion, and induced cell apoptosis and cycle arrest via suppressing the level of TAGLN2 from transcriptional and translational levels and downregulated the expression of proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-2 (MMP-2) in gastric cancer cells. In conclusion, these results demonstrate that decreased expression of miR-133a is associated with the lymph node metastases of patients with gastric cancer. Overexpression of miR-133a inhibits cell growth and invasion and induces cell apoptosis and cycle arrest through repressing TAGLN2 gene, suggesting that miR-133a might be used as a biomarker or therapeutic target for the treatment of gastric cancer.
微小RNA(miRNA)是一类短小且高度保守的非编码RNA,其通过转录后抑制作用调控靶mRNA的基因表达,参与多种恶性肿瘤的发生和发展。尽管miR-133a在某些癌症中已被证明具有肿瘤抑制功能,但miR-133a在胃癌中的临床意义和功能仍不清楚。因此,在本研究中我们聚焦于miR-133a在胃癌发生发展中的表达及机制。研究发现,与癌旁非癌组织(ANCT)相比,原发性胃癌组织中miR-133a的表达下调(P<0.001),而原肌球蛋白-2(TAGLN2)的表达上调(P<0.05)。此外,miR-133a表达降低和TAGLN2表达增加均与胃癌患者的淋巴结转移相关(P<0.001;P=0.011)。功能分析研究表明,miR-133a的异位表达通过从转录和翻译水平抑制TAGLN2的水平,降低了细胞增殖和侵袭能力,并诱导细胞凋亡和细胞周期停滞,同时下调了胃癌细胞中增殖细胞核抗原(PCNA)和基质金属蛋白酶-2(MMP-2)的表达。总之,这些结果表明miR-133a表达降低与胃癌患者的淋巴结转移相关。miR-133a的过表达通过抑制TAGLN2基因抑制细胞生长和侵袭,并诱导细胞凋亡和细胞周期停滞,提示miR-133a可能作为胃癌治疗的生物标志物或治疗靶点。