The NF-κB/miR-488/ERBB2 axis modulates pancreatic cancer cell malignancy and tumor growth through cell cycle signaling.

ABSTRACT: Pancreatic cancer is one of the malignancies having the poorest prognosis due to late diagnoses and lack of efficient treatment regimens. The identification of potential miRNA-targeted gene axes could act as targets for developing novel treatment strategies. Herein, it was assessed that miR-488 expression was markedly downregulated within pancreatic carcinoma. Higher expression of miR-488 was shown to be linked to better prognosis rates of pancreatic carcinoma as per online data. Within two pancreatic tumor cells, MIA PaCa-2 and PANC-1, miR-488 overexpression significantly suppressed malignant cytological behavior by inhibiting cell viability, enhancing cell apoptosis, and inducing cell cycle G2/M-phase arrest. Moreover, miR-488 overexpression also decreased the protein levels of cell cycle regulators, including cyclin A, cyclin B, CDK1, and CDK2. miR-488 directly targets ERBB2 (receptor tyrosine-protein kinase2) to suppress the expression of ERBB2 by targeting its 3'UTR. ERBB2 knockdown in MIA PaCa-2 and PANC-1 cell lines suppressed, but miR-488 inhibition enhanced the cancer cell biological malignant behavior; the effects of miR-488 inhibition on pancreatic cancer cells were significantly reversed by ERBB2 knockdown. NF-κB suppressed the expression of miR-488 transcriptionally via targeting its promoter region, consequentially repressing the tumor-suppressive effects of miR-488 upon pancreatic tumor cells. Thus, an NF-κB/miR-488/ERBB2 axis modulating pancreatic cancer cell malignancy and tumor growth through cell cycle signaling was conclusively demonstrated.

SUBMITTER: Han D 

PROVIDER: S-EPMC8966990 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature