文献类型：期刊文献

英文题名：miR-338-3p Inhibits Apoptosis Evasion in Huh7 Liver Cancer Cells by Targeting Sirtuin 6

作者：Xiao, G.[1];Wang, Q.[1];Ding, M.[1];Zhang, Z.[2];Zhu, W.[1];Chang, J.[1];Fu, Y.[1]

机构：[1]Shaoxing Univ, Affiliated Hosp, Dept Oncol, Shaoxing, Peoples R China;[2]Shaoxing Univ, Affiliated Hosp, Dept Gen Surg, Shaoxing, Peoples R China

年份：2022

卷号：58

期号：5

起止页码：1413

外文期刊名：JOURNAL OF EVOLUTIONARY BIOCHEMISTRY AND PHYSIOLOGY

收录：SCI-EXPANDED(收录号：WOS:000877022600012)、、WOS

基金：This research is supported by the Program from Science and Technology (Medical and Health) of Shaoxing (Grant no. 2020A13061 and no. 2018C30025).

语种：英文

外文关键词：liver cancer; miR-338-3p; apoptosis evasion; Sirtuin 6

外文摘要：Liver cancer is one of the most common cancers with an unsatisfactory prognosis and high mortality rate. The ability of liver cancer cells to evade apoptosis results in the poor therapeutic effect of existing treatments and high rates of tumor recurrence and metastasis. This study investigated the effects of abnormal miR-338-3p expression on the ability of liver cancer cells to avoid apoptosis and the mechanism for that avoidance. The levels of miR-338-3p in liver tumor tissues and in different liver cancer cell lines were analysed by qRT-PCR which demonstrated its downregulation in liver tumor tissues and cells, especially in the Huh7 cells. Cell viability and apoptosis rates of Huh7 liver cancer cells were evaluated using the CCK-8 assay, clone formation assay, flow cytometry, and TUNEL assay. whereas the expression levels of apoptosis-related proteins (Bax, caspase-3, Cyt C, and X-linked inhibitor of apoptosis protein [XIAP]) were analyzed by Western blotting. Next, the target relationship between miR-338-3p and Sirtuin 6 (SIRT6) was identified by conducting a dual luciferase reporter gene assay. Overexpression of miR-338-3p was found to inhibit cell viability and promote the apoptosis of Huh7 cells. Additionally, an upregulation of miR-338-3p significantly promoted Bax, caspase-3, and Cyt C expression, and suppressed XIAP and SIRT6 expression. Notably, SIRT6 was proven to be a target gene of miR-338-3p, and SIRT6 overexpression was shown to reverse the anti-tumor effect of miR-338-3p upregulation in Huh7 cells. Furthermore, the apoptosis induction effect of Cisplatin was reduced by SIRT6, but restored by miR-338-3p. In conclusion, this study demonstrated that miR-338-3p increased apoptosis in liver cancer cell Huh7 by inhibiting SIRT6, and thereby enhanced the cytocidal effect of the apoptosis inducer Cisplatin. These results suggest miR-338-3p as a target for treating liver cancer, which might provide a new therapeutic strategy.