Yao Jian, Zhang Ping, Li Jin, Xu Wei
Department of Integrated Traditional Chinese and Western Medicine, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Oncol Lett. 2017 Jul;14(1):1097-1104. doi: 10.3892/ol.2017.6200. Epub 2017 May 17.
There are accumulating reports that microRNAs are dysregulated in a number of human cancer types, and that they may function as tumor suppressors or oncogenes in tumorigenesis and tumor development. microRNA-215 (miR-215) has been identified as a tumor suppressor in epithelial ovarian, pancreatic, non-small cell lung and colon cancer, whereas it may act as an oncogene in gastric and cervical cancer. The role of miR-215 in breast cancer carcinogenesis and progression has yet to be elucidated. In the present study, the expression level of miR-215 was determined in breast cancer tissues and cell lines using the reverse transcription-quantitative polymerase chain reaction. The effects of miR-215 overexpression on proliferation and the invasive capacity of breast cancer cells were assessed using MTT and cell invasion assays. The results revealed that miR-215 was significantly downregulated in breast cancer tissues and cell lines. Restoration of miR-215 expression inhibited the proliferation and invasion of breast cancer cells. The underlying molecular mechanism for the suppression of proliferation and invasion by miR-215 was investigated. AKT serine/threonine kinase 1 (AKT1) was validated as a novel direct target of miR-215, and the effect of AKT1 small interfering RNA mimicked the effect of miR-215 overexpression in breast cancer cells. These results indicated that miR-215 acted as a tumor suppressor, and that its downregulation in tumor tissues may contribute to the carcinogenesis and progression of breast cancer, indicating that miR-215 may be a novel therapeutic target for the treatment of breast cancer.
越来越多的报道表明，微小RNA在多种人类癌症类型中表达失调，并且它们可能在肿瘤发生和发展过程中作为肿瘤抑制因子或癌基因发挥作用。微小RNA-215（miR-215）已被确定为上皮性卵巢癌、胰腺癌、非小细胞肺癌和结肠癌中的肿瘤抑制因子，而在胃癌和宫颈癌中它可能作为癌基因发挥作用。miR-215在乳腺癌发生和进展中的作用尚未阐明。在本研究中，使用逆转录-定量聚合酶链反应测定乳腺癌组织和细胞系中miR-215的表达水平。使用MTT和细胞侵袭试验评估miR-215过表达对乳腺癌细胞增殖和侵袭能力的影响。结果显示，miR-215在乳腺癌组织和细胞系中显著下调。miR-215表达的恢复抑制了乳腺癌细胞的增殖和侵袭。研究了miR-215抑制增殖和侵袭的潜在分子机制。AKT丝氨酸/苏氨酸激酶1（AKT1）被验证为miR-215的一个新的直接靶点，并且AKT1小干扰RNA的作用模拟了miR-215过表达对乳腺癌细胞的影响。这些结果表明，miR-215作为肿瘤抑制因子发挥作用，其在肿瘤组织中的下调可能有助于乳腺癌的发生和进展，这表明miR-215可能是治疗乳腺癌的一个新的治疗靶点。
