Abstract
Introduction Our work was aimed to explore the mechanisms of MAGI2 antisense RNA 3 (MAGI2-AS3) in regulating hepatocellular carcinoma (HCC) carcinogenesis. Methods MAGI2-AS3, microRNA-519c-3p (miR-519c-3p), and thioredoxin interacting protein (TXNIP) levels in HCC were detected by the RT-qPCR method. Cell proliferation and apoptosis rate were measured using Cell Counting Kit-8 assay and flow cytometry assay. Relationship between MAGI2-AS3, TXNIP, and miR-519c-3p were analyzed via luciferase activity assay, RNA pull-down assay, and RNA immunoprecipitation assay. Mouse xenograft models of HCC were conducted to explore the roles of MAGI2-AS3 in vivo. Results MAGI2-AS3 levels were elevated, and miR-519c-3p decreased in HCC. MAGI2-AS3 overexpression inhibits while its knockdown stimulates HCC cell growth through miR-519c-3p. Moreover, miR-519c-3p overexpression stimulates HCC cell growth. MAGI2-AS3 serves as competing endogenous RNA (ceRNA) of miR-519c-3p to regulate TXNIP in HCC. And, TXNIP upregulation weakened the influence of MAGI2-AS3 knockdown on HCC cell behaviors. Additionally, MAGI2-AS3 overexpression suppressed HCC tumor growth in vivo. Conclusion MAGI2-AS3 inhibits HCC tumorigenesis through miR-519c-3p/TXNIP axis in vitro and in vivo, indicating MAGI2-AS3 plays a crucial role in HCC development.
Highlights
Our work was aimed to explore the mechanisms of MAGI2 antisense RNA 3 (MAGI2-AS3) in regulating hepatocellular carcinoma (HCC) carcinogenesis
We focused on miR-519c-3p which has been revealed that could contribute to HCC growth and metastasis in vitro and in vivo by targeting B cell translocation gene 3 [9]
RT-qPCR analysis showed MAGI2-AS3 expression was remarkedly decreased in HCC tissues compared with adjacent normal tissues (Figure 1(a))
Summary
Our work was aimed to explore the mechanisms of MAGI2 antisense RNA 3 (MAGI2-AS3) in regulating hepatocellular carcinoma (HCC) carcinogenesis. MAGI2-AS3, microRNA-519c-3p (miR-519c-3p), and thioredoxin interacting protein (TXNIP) levels in HCC were detected by the RT-qPCR method. Relationship between MAGI2-AS3, TXNIP, and miR-519c3p were analyzed via luciferase activity assay, RNA pull-down assay, and RNA immunoprecipitation assay. MAGI2-AS3 overexpression inhibits while its knockdown stimulates HCC cell growth through miR519c-3p. MAGI2-AS3 serves as competing endogenous RNA (ceRNA) of miR-519c-3p to regulate TXNIP in HCC. TXNIP upregulation weakened the influence of MAGI2-AS3 knockdown on HCC cell behaviors. MAGI2-AS3 overexpression suppressed HCC tumor growth in vivo. MAGI2-AS3 inhibits HCC tumorigenesis through miR-519c-3p/TXNIP axis in vitro and in vivo, indicating MAGI2-AS3 plays a crucial role in HCC development. The improvements are on treatment methods, the prognosis of liver cancer remains poor due to most patients are diagnosed at advanced stages [2]. Only some of these lncRNAs have been functionally characterized, they are found to contribute the malignant behaviors of cancer cells and could not be merely regarded as transcriptional “noise” [5]
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