科研之友
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摘要
Backgrounds: Sorafenib-resistance leads to poor prognosis and high mortality in advanced hepatocellular carcinoma (HCC), and this study aims to investigate the functional role of a circular RNA ITCH (circITCH) in regulating the sorafenib-resistance of HCC and its underlying mechanisms. @@@ Methods: The expression of circITCH in HCC tissues and cell lines were detected by performing quantitative realtime polymerase chain reaction. Sorafenib-resistant HCC cells were transfected with PLCDH-circITCH to upregulate circITCH and intervened with sorafenib, and MTT assay, flow cytometry and transwell assay were used to test the cell viability, apoptosis and migration ability, respectively. The downstream target of circITCH were explored by using bioinformatic analysis, dual luciferase reporter system and Western blot. @@@ Results: CircITCH was significantly down-regulated in HCC tissues and cell lines, compared with their normal counterparts. Especially, in contrast with the sorafenib-sensitive HCC cells, continuous sorafenib treatment decreased the expression levels of circITCH in the sorafenib-resistant HCC cells. Overexpression of circITCH increased sorafenib-sensitivity, promoted cell apoptosis and reduced cell migration abilities in the sorafenibresistant HCC cells. Mechanically, circITCH elevated PTEN expression to inactivate the PI3K/Akt signals through negatively regulating miR-20b-5p in HCC, and upregulating miR-20b-5p or inhibiting PTEN abolished the enhancing effect of circITCH overexpression on sorafenib-induced cytotoxicity in sorafenib-resistant HCC cells. @@@ Conclusion: Taken together, this study proves that circITCH enhances sorafenib-sensitivity in sorafenib-resistant HCC cells via regulating the miR-20b-5p/PTEN/PI3K/Akt signaling cascade, which highlights the potential value of circITCH as a target for enhancing the sorafenib-sensitivity in HCC.
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单位哈尔滨医科大学
