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GSG2 knockdown suppresses cholangiocarcinoma progression by regulating cell proliferation, apoptosis and migration.

ABSTRACT: Cholangiocarcinoma (CCA) is the second most common type of hepatocellular carcinoma characterized by high aggressiveness and extremely poor patient prognosis. The germ cell‑specific gene 2 protein (GSG2) is a histone H3 threonine‑3 kinase required for normal mitosis. Nevertheless, the role and mechanism of GSG2 in the progression and development of CCA remain elusive. In the present study, the association between GSG2 and CCA was elucidated. Firstly, we demonstrated that GSG2 was overexpressed in CCA specimens and HCCC‑9810 and QBC939 cells by immunohistochemical (IHC) staining. It was further revealed that high expression of GSG2 in CCA had significant clinical significance in predicting disease deterioration. Subsequently, cell proliferation, apoptosis, cell cycle distribution and migration were measured by MTT, flow cytometry, and wound healing assays, respectively in vitro. The results demonstrated that downregulation of GSG2 decreased proliferation, promoted apoptosis, arrested the cell cycle and weakened migration in the G2 phase of CCA cells. Additionally, GSG2 knockdown inhibited CCA cell migration by suppressing epithelial‑mesenchymal transition (EMT)‑related proteins, such as N‑cadherin and vimentin. Mechanistically, GSG2 exerted effects on CCA cells by modulating the PI3K/Akt, CCND1/CDK6 and MAPK9 signaling pathways. In vivo experiments further demonstrated that GSG2 knockdown suppressed tumor growth. In summary, GSG2 was involved in the progression of CCA, suggesting that GSG2 may be a potential therapeutic target for CCA patients.

SUBMITTER: Zhou J

PROVIDER: S-EPMC8042665 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Long non‑coding RNAs (lncRNAs) have been validated to mediate the development of atherosclerosis (AS). In the present study, the molecular mechanisms and functions of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in the advancement of human aortic endothelial cells (HAECs) were investigated. The levels of lncRNA‑NEAT1 and miR‑638 expression in clinical samples and cells were explored via quantitative reverse transcription polymerase chain reaction. Colony formation and CCK‑8 assays were performed to determine the proliferative capacity of cells, and the apoptotic capacity of cells was analyzed on the basis of apoptotic cell proportion and caspase‑3 activity. Then, the proportion of cells and correlations among phosphoglycerate kinase 1 (PGK1), NEAT1, and miR‑638 were determined through RNA immunoprecipitation and luciferase assays and bioinformatics analysis. Moreover, the expression levels of Ki‑67, proliferating cell nuclear antigen, PGK1, Bax, Bcl‑2, (p)‑mTOR, (p)‑AKT, and β‑catenin were analyzed via western blot analysis. In the serum of patients with AS and HAECs induced by oxidized low‑density lipoprotein (ox‑LDL), the expression level of miR‑638 was decreased, whereas that of NEAT1 was increased. After ox‑LDL therapy, NEAT1 knockdown suppressed HAEC proliferation and stimulated HAEC apoptosis, which could be reversed by the miR‑638 inhibitor. NEAT1 inhibited miR‑638 expression through direct mutual action. The following mechanical investigations revealed that PGK1 was a miR‑638 target, whose expression was increased by NEAT1, a competing endogenous RNA of miR‑638. Additionally, the miR‑638 inhibitor contributed to proliferation and suppressed apoptosis through the activation of the AKT/mTOR signaling pathway in ox‑LDL‑induced HAECs. NEAT1 adjusted the AKT/mTOR signaling pathway via miR‑638 in ox‑LDL‑induced HAECs to accelerate their proliferation and impede their apoptosis. This result revealed that NEAT1 may be valuable in the treatment of AS.

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GSG2 knockdown suppresses cholangiocarcinoma progression by regulating cell proliferation, apoptosis and migration.

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