MicroRNA-874 inhibits growth, induces apoptosis and reverses chemoresistance in colorectal cancer by targeting X-linked inhibitor of apoptosis protein (Retracted article. See vol. 47, pg. 69, 2022)
MicroRNA-874 inhibits growth, induces apoptosis and reverses chemoresistance in colorectal cancer by targeting X-linked inhibitor of apoptosis protein (Retracted article. See vol. 47, pg. 69, 2022)
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DOI：
10.3892/or.2016.4810
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发表时间：
2016-07-01
期刊：
影响因子：
4.2
通讯作者：
Pan, Weiyun
中科院分区：
文献类型：
--
作者：
Han, Jinfeng;Liu, Zhongmin;Pan, Weiyun
MicroRNA-874（miR-874）在几种类型的癌症中下调并作为肿瘤抑制因子，而miR-874在结直肠癌（CRC）中的生物学功能仍不清楚。本研究的目的是探讨miR-874在结直肠癌中的临床意义、生物学效应和潜在机制。采用逆转录-定量PCR（RT-qPCR）检测CRC细胞系和组织样本中miR-874的表达。采用MTT法、集落形成实验和流式细胞术分析miR-874表达对大肠癌细胞生长、凋亡和耐药性的影响。通过双荧光素酶报告基因测定确定推定的miR-874靶标的调节。采用RT-qPCR和Western blot方法检测XIAP mRNA和蛋白表达水平。发现miR-874在结直肠癌组织和细胞系中表达下调，其表达与结直肠癌患者的TNM分期和淋巴结转移呈显著负相关。功能分析显示，miR-874的恢复抑制CRC细胞的增殖，减少集落形成，增强凋亡，以及降低5-氟尿嘧啶（5-FU）抗性。通过荧光素酶活性测定、RT-qPCR和western blot分析，显示XIAP是miR-874的直接靶点。此外，XIAP在CRC组织和细胞系中的表达显著增加，并且与miR-874表达呈负相关。重要的是，XIAP在CRC细胞中的下调具有与miR-874过表达相似的作用。综上所述，这些数据表明，miR-874通过靶向XIAP抑制CRC细胞的生长，增加细胞凋亡并增强化疗敏感性，表明miR-874可能是治疗人类CRC的潜在分子靶标。
MicroRNA-874 (miR-874) is downregulated and acts as a tumor suppressor in several types of cancers, whereas the biological function of miR-874 in colorectal cancer (CRC) remains unclear. The aims of the present study were to investigate the clinical significance, biological effects, and the underlying mechanisms of miR-874 in CRC. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect miR-874 expression in CRC cell lines and tissue samples. MTT and colony formation assays and flow cytometry were performed to analyze the effects of miR-874 expression on growth, apoptosis and the chemoresistance of CRC cells. Regulation of putative miR-874 targets was determined by dual-luciferase reporter assays. RT-qPCR and western blot assays were performed to detected the levels of X-linked inhibitor of apoptosis protein (XIAP) mRNA and protein expression. It was found that expression of miR-874 was downregulated in CRC tissues and cell lines, and its expression was significantly negatively correlated with TNM stage and lymph node metastasis of the CRC patients. Functional assays revealed that restoration of miR-874 inhibited proliferation, reduced colony formation, enhanced apoptosis, as well as decreased the 5-fluorouracil (5-FU) resistance of the CRC cells. Through luciferase activity assay, RT-qPCR and western blot analysis, XIAP was shown to be a direct target of miR-874. In addition, XIAP expression was significantly increased in the CRC tissues and cell lines, and was inversely correlated with miR-874 expression. Importantly, downregulation of XIAP in CRC cells had an effect similar to that of miR-874 overexpression. Taken together, these data showed that miR-874 inhibits growth, increases apoptosis and enhances chemosensitivity in CRC cells by targeting XIAP, suggesting that miR-874 may be a potential molecular target for the treatment of human CRC.