Mei Xu1,2, Kai Zhou3, Yuanzhe Wu2, Li Wang2, Su Lu4. 1. Major in Traditional Medicine of Gynecology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. 2. Department of Gynecology and Obstetrics, Nanjing General Hospital, Nanjing, Jiangsu, China. 3. Department of Urology, Nanjing General Hospital, Nanjing, Jiangsu, China. 4. Department of Gynecology and Obstetrics, Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing, Jiangsu, China.
Abstract
This study aimed to investigate the regulatory mechanism of linc00161/miR-128/MAPK1 axis on drug resistance of ovarian cancer. Methods: the differentially expressed lncRNAs were screened based on microarray analysis. The expression of linc00161, miR-128 and MAPK1 in ovarian cancer-resistant tissues and cells was tested qRT-PCR, whereas MAPK1 protein expression was examined via western blot in the ovarian cancer resistant cells. The targeted relationship between miR-128 and linc00161 as well as the relationship between miR-128 and MAPK1 were testified by Dual luciferase gene reporter assay. The influence of miR-128 and MAPK1 on the proliferation of ovarian cancer-resistant cells was demonstrated by CCK-8 and colony formation assay. The effect of linc00161 on ovarian cancer was demonstrated by xenograft tumor model in vivo. Results: Linc00161 was highly expressed in ovarian cancer-resistant tissues and SKOV3/DDP cells while the miR-128 displayed a lower expression. Overexpression of linc00161 increased the colony formation ratio in SKOV3 cells, whereas sh-linc00161 reduced colony formation ratio in SKOV3/DDP cells. MAPK1 was highly expressed in ovarian cancer-resistant tissues and cells and could be regulated by linc00161 and miR-128. The proliferation ability of SKOV3 cell was enhanced after transfected with miR-128 inhibitor, whereas that of SKOV3/DDP cells was attenuated by miR-128 mimics. In addition, the colony formation ratio of SKOV3 cells co-transfected with DDP + MAPK1 + sh-linc00161 decreased. The colony formation ratio of SKOV3/DDP cells also declined after transfected with DDP+ MAPK1. Linc00161 regulated the drug resistance of ovarian cancer via modulating microRNA-128/MAPK1. In vivo, sh-linc00161 inhibited the tumor growth.
This study aimed to investigate the regulatory mechanism of linc00161/miR-128/MAPK1 axis on drug resistance of ovarian cancer. Methods: the differentially expressed lncRNAs were screened based on microarray analysis. The expression of linc00161, miR-128 and MAPK1 in ovarian cancer-resistant tissues and cells was tested qRT-PCR, whereas MAPK1 protein expression was examined via western blot in the ovarian cancer resistant cells. The targeted relationship between miR-128 and linc00161 as well as the relationship between miR-128 and MAPK1 were testified by Dual luciferase gene reporter assay. The influence of miR-128 and MAPK1 on the proliferation of ovarian cancer-resistant cells was demonstrated by CCK-8 and colony formation assay. The effect of linc00161 on ovarian cancer was demonstrated by xenograft tumor model in vivo. Results:Linc00161 was highly expressed in ovarian cancer-resistant tissues and SKOV3/DDP cells while the miR-128 displayed a lower expression. Overexpression of linc00161 increased the colony formation ratio in SKOV3 cells, whereas sh-linc00161 reduced colony formation ratio in SKOV3/DDP cells. MAPK1 was highly expressed in ovarian cancer-resistant tissues and cells and could be regulated by linc00161 and miR-128. The proliferation ability of SKOV3 cell was enhanced after transfected with miR-128 inhibitor, whereas that of SKOV3/DDP cells was attenuated by miR-128 mimics. In addition, the colony formation ratio of SKOV3 cells co-transfected with DDP + MAPK1 + sh-linc00161 decreased. The colony formation ratio of SKOV3/DDP cells also declined after transfected with DDP+ MAPK1. Linc00161 regulated the drug resistance of ovarian cancer via modulating microRNA-128/MAPK1. In vivo, sh-linc00161 inhibited the tumor growth.
Authors: Eleonora A Braga; Marina V Fridman; Alexey A Moscovtsev; Elena A Filippova; Alexey A Dmitriev; Nikolay E Kushlinskii Journal: Int J Mol Sci Date: 2020-11-23 Impact factor: 5.923
Authors: Jingchun Qu; Hui-Qi Qu; Jonathan P Bradfield; Joseph T Glessner; Xiao Chang; Lifeng Tian; Michael March; John J Connolly; Jeffrey D Roizen; Patrick M A Sleiman; Hakon Hakonarson Journal: Sci Rep Date: 2021-08-06 Impact factor: 4.379