Department of Urinary Surgery, The Affiliated Hospital, Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China.
Department of Medical Insurance, Jilin Academy of Chinese Medicine Sciences, Changchun, Jilin 130021, P.R. China.
Mol Med Rep. 2018 Jan;17(1):1361-1367. doi: 10.3892/mmr.2017.7956. Epub 2017 Nov 3.
MicroRNA‑212 (miR‑212) has been observed to be significantly deregulated in various types of human cancer. However, the clinical significance of miR‑212 and the associated molecular signaling pathways involved in the progression of renal cell carcinoma (RCC) remain unclear. In the present study, miR‑212 expression was significantly downregulated in RCC tissues compared with adjacent non‑tumor tissues. Clinical association analysis indicated that low expression of miR‑212 was prominently associated with large tumor size, advanced tumor, nodes, metastasis stage and lymph node metastasis. In vitro studies revealed that upregulation of miR‑212 inhibited cell proliferation, migration and invasion, and induced apoptosis in Caki‑1 cells. Forkhead box protein A1 (FOXA1) was identified as a direct target of miR‑212 in RCC cells via luciferase reporter assays and western blotting. In addition, FOXA1 expression was upregulated in RCC tissues compared with adjacent noncancerous tissues. An inverse correlation between FOXA1 and miR‑212 expression was observed in RCC tissues. Notably, FOXA1 overexpression partially rescued miR‑212‑mediated inhibition of cell proliferation, migration and invasion in RCC cells. These results suggested that miR‑212 suppresses RCC proliferation and invasion by modulating FOXA1, suggesting that miR‑212 may have potential as a therapeutic target in RCC.
微小 RNA-212（miR-212）在各种人类癌症中均存在明显失调。然而，miR-212 的临床意义及其在肾细胞癌（RCC）进展中涉及的相关分子信号通路仍不清楚。在本研究中，与相邻非肿瘤组织相比，RCC 组织中 miR-212 的表达显著下调。临床相关性分析表明，miR-212 低表达与肿瘤体积大、肿瘤进展、淋巴结转移和淋巴结转移明显相关。体外研究表明，miR-212 的上调抑制了 Caki-1 细胞的增殖、迁移和侵袭，并诱导其凋亡。荧光素酶报告基因检测和 Western blot 分析表明，FOXA1 是 RCC 细胞中 miR-212 的直接靶基因。此外，与相邻非癌组织相比，RCC 组织中 FOXA1 的表达上调。在 RCC 组织中观察到 FOXA1 和 miR-212 表达呈负相关。值得注意的是，FOXA1 的过表达部分挽救了 miR-212 对 RCC 细胞增殖、迁移和侵袭的抑制作用。这些结果表明，miR-212 通过调节 FOXA1 抑制 RCC 的增殖和侵袭，表明 miR-212 可能在 RCC 中具有作为治疗靶点的潜力。
