Cancer Immunity Research Laboratory, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, Tianjin 300211, P.R. China.
School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China.
Int J Mol Med. 2018 Feb;41(2):1021-1029. doi: 10.3892/ijmm.2017.3269. Epub 2017 Nov 17.
The present study aimed to explore the effects of microRNA (miRNA)‑30a‑5p on tumor proliferation and to seek a potential therapeutic target for the treatment of human renal cancer. The results demonstrated that the expression levels of miRNA‑30a‑5p were reduced in tumor samples from patients with renal cancer compared with in normal tissue samples. Overall survival and disease‑free survival were increased in patients with renal cancer and high miRNA‑30a‑5p expression compared with in those with low miRNA‑30a‑5p. Furthermore, overexpression of miRNA‑30a‑5p suppressed cell proliferation, induced apoptosis, and promoted caspase‑3/9 activities and B‑cell lymphoma 2‑associated X protein (Bax) protein expression in Caki‑2 cells. In addition, the results confirmed that overexpression of miRNA‑30a‑5p inhibited metadherin (MTDH), upregulated phosphatase and tensin homolog (PTEN) and suppressed phosphorylated (p)‑protein kinase B (AKT) protein expression levels in Caki‑2 cells. Furthermore, transfection with small interfering RNA‑MTDH, increased the effects of miRNA‑30a‑5p on the inhibition of cell proliferation, and promotion of apoptosis, caspase‑3/9 activities and Bax protein expression levels in Caki‑2 cells. Knockdown of MTDH expression also upregulated PTEN and suppressed p‑AKT protein expression in Caki‑2 cells. In conclusion, the present study is the first, to the best of our knowledge, to provide evidence suggesting that miRNA‑30a‑5p suppresses tumor human renal cancer cell proliferation via the MTDH/PTEN/AKT pathway.
本研究旨在探讨 microRNA（miRNA）-30a-5p 对肿瘤增殖的影响，并寻求一种治疗人类肾癌的潜在治疗靶点。结果表明，与正常组织样本相比，肾癌患者肿瘤样本中的 miRNA-30a-5p 表达水平降低。与 miRNA-30a-5p 低表达的患者相比，miRNA-30a-5p 高表达的肾癌患者的总生存率和无病生存率均增加。此外，miRNA-30a-5p 的过表达抑制了 Caki-2 细胞的增殖，诱导了细胞凋亡，并促进了半胱氨酸天冬氨酸蛋白酶 3/9（caspase-3/9）的活性和 B 细胞淋巴瘤 2 相关 X 蛋白（Bax）的表达。此外，研究结果证实，miRNA-30a-5p 的过表达抑制了间甲基二氢叶酸还原酶（MTDH）的表达，上调了磷酸酶和张力蛋白同源物（PTEN）的表达，并抑制了 Caki-2 细胞中磷酸化（p）蛋白激酶 B（AKT）的表达水平。此外，用小干扰 RNA-MTDH 转染可增强 miRNA-30a-5p 对 Caki-2 细胞增殖抑制和促进细胞凋亡、caspase-3/9 活性和 Bax 蛋白表达水平的影响。下调 MTDH 表达也上调了 Caki-2 细胞中 PTEN 的表达并抑制了 p-AKT 蛋白的表达。综上所述，本研究首次提供证据表明，miRNA-30a-5p 通过 MTDH/PTEN/AKT 通路抑制肿瘤人肾癌细胞的增殖。
