Regulation of Tumorigenesis in Hepatocellular Carcinoma via the AKT3 Pathway in Cell Lines

Abstract

Background. The estimation of hepatocellular carcinoma (HCC) is tremendously inferior because of the formation of chemoresistance, integrated with essentially increased stemness belongings. At present, the relevance between miR-122 and cancer development was mostly undisclosed with single study reflecting its importance in glioblastoma. Material and Methods. The research here was focused to investigate the task of miR-122 to modulate tumorigenesis in hepatocellular carcinoma by aiming AKT3 in the management of hepatocellular carcinoma stemness and chemosensitivity. The method of QRT-PCR was performed to investigate the aspect of miR-122 and AKT3 in tissue sample and cell lines. The evaluation was done using gain- or loss-of-function in order to retrieve the function of miR-122 in the hepatocellular carcinoma cells, including cell multiplication and stemness effects. The properties of hepatocellular carcinoma were discovered by the development of sphere development, cell feasibility, and the emergence of colony. RNA immunoprecipitation (RIP), luciferase reporter, and the RNA pull down evaluation were conducted to investigate the communication between the miR-122 and AKT3. Therefore, a naked mouse xenograft specimen was set up for the in vivo analysis. Results. Here, we determined the new role of AKT3 and unmediated target of miR-122. The reimposition of miR-122 appearance in the hepatocellular carcinoma cell lines reduces the levels of AKT3 and also hinders the relocation and expansion of cells by prompting apoptosis. These phenotypes are antitumor in nature and can be retrieved by the reorganization of the AKT3 expression which signals the crucial role of AKT3 in the miR-122 arbitrated HCC modification. The in vivo analysis demonstrated the reimposition of miR-122 entirely obstructing the xenograft expansion to manage tumorigenesis in hepatocellular carcinoma and a prospective remedial entrant for the liver cancer. Conclusion. In this study, it was observed that miR-122 encourages the stemness role of hepatocellular carcinoma and diminishes the chemosensitivity by cleaning the miR-122 in order to initiate the AKT3. The in vivo study reflected the restoration of miR-122 which completely hinders the xenograft growth to regulate the tumorigenesis in the HCC.

The Multifunctional Nature of the MicroRNA/AKT3 Regulatory Axis in Human Cancers

“…The deregulation and activation of the AKT signaling pathway is common in HCC and is associated with poor patient prognosis. AKT3 expression is upregulated in the HCC cell lines SNU-182, Hep3B2, and SNU-475 [67]. Furthermore, a growing number of HCC-associated genes are being found to be regulated by ncRNAs.…”

“…MiR-122, the most highly expressed miRNA in the healthy adult liver, is responsible for liver stem cell differentiation towards the hepatocyte lineage. Its expression is frequently lost in HCC tissues and HCC cell lines [67,68]. By binding the 3 -UTR of AKT3 and controlling AKT3 gene expression, miR-122 inhibits HCC cell proliferation, increases the chemosensitivity of HCC cells, and attenuates HCC tumor growth in vivo [67,68].…”

“…Its expression is frequently lost in HCC tissues and HCC cell lines [67,68]. By binding the 3 -UTR of AKT3 and controlling AKT3 gene expression, miR-122 inhibits HCC cell proliferation, increases the chemosensitivity of HCC cells, and attenuates HCC tumor growth in vivo [67,68]. The forced overexpression of miR-144, miR-424, or miR-582-5p in HCC cells results in anti-HCC effects, by suppressing cell proliferation, migration, invasion, or survival [69][70][71].…”

Retracted: Regulation of Tumorigenesis in Hepatocellular Carcinoma via the AKT3 Pathway in Cell Lines

“…This article has been retracted by Hindawi, as publisher, following an investigation undertaken by the publisher [ 1 ]. This investigation has uncovered evidence of systematic manipulation of the publication and peer-review process.…”