Chen Yongsheng, Liu Wenhua, Li Dechao, Cao Yan, Wang Wentao, Li Changfu, An Ruihua
Department of Urology, Harbin Medical University Cancer Hospital, Harbin, China.
Intensive Care Unit (ICU) Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Transl Androl Urol. 2022 Jul;11(7):996-1006. doi: 10.21037/tau-22-464.
We aimed to explore miR-148a exerts a tumor suppressor effect and arsenic trioxide (AsO) sensitivity on renal cell carcinoma (RCC).
We performed polymerase chain reaction (PCR) on 42 pairs of tumor and paracancerous samples collected from RCC patients to investigate the miR-148a expression; meanwhile, we analyzed the interplay between clinical indicators and miR-148a expression of RCC. Then, the influence of miR-148a overexpression on the functions of RCC cells were analyze using transwell migration assay, Cell Counting Kit-8 (CCK-8), and cell wound healing assay. Furthermore, the ability of miR-148a to sensitize Caki-1 cells treated with AsO were detected using flow cytometry. Finally, the relevant mechanism of miR-148a on the downstream gene Wnt family member 10A () was explored by cell reverse method.
The results from RCC patients indicated a significantly lower miR-148a level than adjacent tissues. The low miR-148a expression increased prevalence of distant metastasis and decreased survival rate compared to those with high expression in patients. In the RCC cell lines, the proliferation and metastasis ability of the miR-148a mimic group was remarkably lower than the miR-NC group. At the same time, it was verified that was remarkably higher cell lines and RCC tissues; and negatively related to miR-148a expression. In addition, miR-148a mimics were found to remarkably reduce the protein expression of . In the cell reverse experiment, overexpression of was confirmed to offset the miR-148a mimics effect on metastasis and proliferation of RCC cells. In addition, an increase in relative apoptosis was detected in AsO treated with/without miR-148a mimics for 48 hours, and apoptosis was significantly reduced after transfection with in the Caki-1 cell line and significantly reduced after combined treatment.
The study revealed that miR-148a is associated with distant metastases and leads to poor prognosis in RCC patients. Moreover, miR-148a inhibit the malignant progression and increase the sensitivity of RCC cells to AsO by regulating .
我们旨在探讨miR-148a对肾细胞癌（RCC）发挥肿瘤抑制作用及三氧化二砷（AsO）敏感性的影响。
我们对从RCC患者收集的42对肿瘤和癌旁样本进行聚合酶链反应（PCR），以研究miR-148a的表达；同时，分析RCC临床指标与miR-148a表达之间的相互作用。然后，使用Transwell迁移实验、细胞计数试剂盒-8（CCK-8）和细胞划痕愈合实验分析miR-148a过表达对RCC细胞功能的影响。此外，使用流式细胞术检测miR-148a使经AsO处理的Caki-1细胞致敏的能力。最后，通过细胞反向法探索miR-148a对下游基因Wnt家族成员10A（）的相关机制。
RCC患者的结果表明，miR-148a水平显著低于相邻组织。与高表达患者相比，低miR-148a表达增加了远处转移的发生率并降低了生存率。在RCC细胞系中，miR-148a模拟物组的增殖和转移能力明显低于miR-NC组。同时，证实细胞系和RCC组织中显著更高；且与miR-148a表达呈负相关。此外，发现miR-148a模拟物显著降低的蛋白表达。在细胞反向实验中，证实的过表达可抵消miR-148a模拟物对RCC细胞转移和增殖的影响。此外，在用/不用miR-148a模拟物处理48小时的AsO中检测到相对凋亡增加，在Caki-1细胞系中转染后凋亡显著减少，联合处理后凋亡也显著减少。
该研究表明，miR-148a与远处转移相关，并导致RCC患者预后不良。此外，miR-148a通过调节抑制RCC细胞的恶性进展并增加其对AsO的敏感性。
