miR-125b-5p inhibits cell proliferation by targeting ASCT2 and regulating the PI3K/AKT/mTOR pathway in an LPS-induced intestinal mucosa cell injury model.
miR-125b-5p inhibits cell proliferation by targeting ASCT2 and regulating the PI3K/AKT/mTOR pathway in an LPS-induced intestinal mucosa cell injury model.
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在 LPS 诱导的肠粘膜细胞损伤模型中，miR-125b-5p 通过靶向 ASCT2 并调节 PI3K/AKT/mTOR 通路抑制细胞增殖
DOI：
10.3892/etm.2021.10270
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发表时间：
2021-08
影响因子：
2.7
通讯作者：
Wang K
中科院分区：
文献类型：
--
作者：
Guo H;Gao J;Qian Y;Wang H;Liu J;Peng Q;Zhou Y;Wang K
Intestinal barrier injury is an important cause of death in patients with acquired immune deficiency syndrome (AIDS). Therefore, it is of great significance to identify a therapeutic target for intestinal barrier injury to delay the progression of AIDS. microRNA (miRNA/miR)-125b-5p has an extensive role in cancer and controlling intestinal epithelial barrier function, but its role in human immunodeficiency virus-related intestinal mucosal damage remains unknown. The present study was designed to explore the effects of miR-125b-5p on lipopolysaccharide (LPS)-induced intestinal mucosal injury and the underlying mechanism. The expression of miR-125b-5p and ASCT2 mRNA was detected in colon biopsy samples of 10 patients with AIDS and 10 control healthy subjects. Human intestinal embryonic mucosa cells (CCC-HIE-2) were used to establish an LPS-induced intestinal mucosa cell injury model in vitro. Cell proliferation and apoptosis were determined by MTT assays and flow cytometry, respectively. miR-125b-5p levels and ASCT2 mRNA and protein expression levels in the LPS-induced intestinal mucosa cell injury model were detected by reverse transcription-quantitative PCR (RT-qPCR) and western blotting. The interaction between miR-125b-5p and ASCT2 was analyzed using a dual luciferase reporter assay. The results demonstrated that miR-125b-5p levels were increased and ASCT2 mRNA expression levels were decreased in colon samples from patients with AIDS and in LPS-induced intestinal mucosa cells. In the LPS-induced intestinal mucosa cell injury model, transfection with miR-125b-5p mimic inhibited cell proliferation and promoted cell apoptosis, while transfection with a miR-125b-5p inhibitor increased cell proliferation and attenuated cell apoptosis. Furthermore, miR-125b-5p mimic transfection resulted in a decrease of ASCT2 mRNA and protein expression, whereas the inhibitor increased ASCT2 mRNA and protein expression. Dual luciferase reporter assays suggested that ASCT2 was a direct target of miR-125b-5p, and its restoration weakened the effect of miR-125b-5p on LPS-induced intestinal mucosa cell injury. Transfection with the miR-125b-5p mimic also exhibited a suppressive effect on the PI3K/AKT/mTOR pathway in the LPS-induced intestinal mucosal cell injury model. Overall, the present study indicated that miR-125b-5p accelerated LPS-induced intestinal mucosa cell injury by targeting ASCT2 and upregulating the PI3K/AKT/mTOR pathway. The current findings may provide novel targets for the treatment of intestinal barrier injury in patients with AIDS.
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影响因子：
14.2
作者：
Groschwitz, Katherine R.;Hogan, Simon P.
通讯作者：
Hogan, Simon P.
影响因子：
6.1
作者：
Chen Shi-da;Chen Ya-bin;Tan Zhi
通讯作者：
Tan Zhi
DOI：
10.1016/j.jss.2009.03.066
发表时间：
2009-09
期刊：
The Journal of surgical research
影响因子：
--
作者：
Costantini TW;Peterson CY;Kroll L;Loomis WH;Eliceiri BP;Baird A;Bansal V;Coimbra R
通讯作者：
Coimbra R
影响因子：
4.2
作者：
Guo, Huiming;Xu, Yu;Wang, Kunhua
通讯作者：
Wang, Kunhua
影响因子：
6.7
作者：
Estes JD;Harris LD;Klatt NR;Tabb B;Pittaluga S;Paiardini M;Barclay GR;Smedley J;Pung R;Oliveira KM;Hirsch VM;Silvestri G;Douek DC;Miller CJ;Haase AT;Lifson J;Brenchley JM
通讯作者：
Brenchley JM