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Circ5912 suppresses cancer progression via inducing MET in bladder cancer.

ABSTRACT: BACKGROUND:Increasing evidence suggests that circular RNAs play a key role in regulating bladder cancer progression. However, this remains to be fully elucidated. RESULTS:In this study, we reanalyzed our previous RNA sequence, and circ5912 was found to downregulate significantly in bladder cancer tissues compared with normal control. Expression of circ5912 inversely correlates with bladder cancer grade, stage, metastasis, and better patient outcomes. In vitro and in vivo, circ5912 has been shown to repress transforming growth factor ? signaling, which suppresses proliferation, invasion and migration of bladder cancer induced by mesenchymal-to epithelial transition. CONCLUSIONS:Our study firstly demonstrate that circ5912 regulates mesenchymal-to epithelial transition pathway to suppress bladder cancer progression and propose new therapeutic targets and biomarkers for bladder cancer. MATERIALS AND METHODS:Clinical values of circ5912 in human bladder cancer were examined in a cohort of 58 patients by qPCR. 2 bladder cancer cell lines, T24 and SW780, were used for biological evaluation of circ5912. CCK8, clone formation, wound healing and trans-well assays were performed to determine the in vivo effect of circ5912; a mouse subcutaneous model was designed for in vivo analysis. Western blotting, RNA pulldown assays and florescent in situ hybridization were applied for mechanistic analysis.

SUBMITTER: Su Y

PROVIDER: S-EPMC6932894 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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circ5912 suppresses cancer progression via inducing MET in bladder cancer.

Su Yinjie Y Du Zehu Z Zhong Guanglei G Ya Yiyao Y Bi Junming J Shi Juanyi J Chen Luping L Dong Wen W Lin Tianxin T

Aging 20191205 23

<h4>Background</h4>Increasing evidence suggests that circular RNAs play a key role in regulating bladder cancer progression. However, this remains to be fully elucidated.<h4>Results</h4>In this study, we reanalyzed our previous RNA sequence, and circ5912 was found to downregulate significantly in bladder cancer tissues compared with normal control. Expression of circ5912 inversely correlates with bladder cancer grade, stage, metastasis, and better patient outcomes. <i>In vitro</i> and <i>in vivo ...[more]

PMID: 31808751

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Project description:PurposeBreast cancer is the most frequent cancer in women with significant death rate. Morbidity is associated with drug resistance and metastasis. Development of novel drugs is unmet need. The aim of this study is to show potent anti-neoplastic activity of the UM171 compound on breast cancer cells and its mechanism of action.MethodsThe inhibitory effect of UM171 on several breast cancer (BC) cell lines was examined using MTT and colony-forming assays. Cell cycle and apoptosis assays were utilized to determine the effect of UM171 on BC cell proliferation and survival. Wound healing scratch and transwell migration assays were used to examine the migration of BC cell lines in culture. Xenograft of mouse model with 4T1 cells was used to determine inhibitory effect of UM171 in vivo. Q-RT-PCR and western blotting were used to determine the expression level of genes effected by UM171. Lentivirus-mediated shRNAs were used to knockdown the expression of KLF2 in BC cells.ResultsUM171 was previously identified as a potent agonist of human hematopoietic stem cell renewal and inhibitor of leukemia. In this study, UM171 was shown to inhibit the growth of multiple breast cancer cell lines in culture. UM171-mediated growth inhibition was associated with the induction of apoptosis, G2/M cell cycle arrest, lower colony-forming capacity, and reduced motility. In a xenotransplantation model of mouse triple-negative breast cancer 4T1 cells injected into syngeneic BALB/c mice, UM171 strongly inhibited tumor growth at a level comparable to control paclitaxel. UM171 increased the expression of the three PIM genes (PIM1-3) in breast cancer cells. Moreover, UM171 strongly induced the expression of the tumor suppressor gene KLF2 and cell cycle inhibitor P21CIP1. Accordingly, knockdown of KLF2 using lentivirus-mediated shRNA significantly attenuated the growth suppressor activity of UM171. As PIM1-3 act as oncogenes and are involved in breast cancer progression, induction of these kinases likely impedes the inhibitory effect of KLF2 induction by UM171. Accordingly, combination of UM171 with a PAN-PIM inhibitor LGH447 significantly reduced tumor growth in culture.ConclusionThese results suggested that UM171 inhibited breast cancer progression in part through activation of KLF2 and P21. Combination of UM171 with a PAN-PIM inhibitor offer a novel therapy for aggressive forms of breast cancer.

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Circ5912 suppresses cancer progression via inducing MET in bladder cancer.

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circ5912 suppresses cancer progression via inducing MET in bladder cancer.

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