VPS33B modulates c-Myc/p53/miR-192-3p to target CCNB1 suppressing the growth of non-small cell lung cancer

Abstract

VPS33B is reported to be a tumor suppressor in hepatocellular carcinoma, nasopharyngeal carcinoma, colon cancer, and lung adenocarcinoma. Here, we observed that reduced VPS33B protein level was an unfavorable factor that promoted the pathogenesis of non-small cell lung cancer (NSCLC) in clinical specimens. We achieved lentivirus-mediated stable overexpression of VPS33B in NSCLC cells. Increased VPS33B reduced cell cycle transition and cell proliferation of NSCLC cells in vivo and in vitro. Knocking down VPS33B restored cell growth. Mechanism analysis indicated that miR-192-3p was induced by VPS33B and acted as a tumor suppressor of cell growth in NSCLC. Further, c-Myc or p53 was identified as a transcription factor that bound to the miR-192-3p promoter and regulated its expression. miR-192-3p directly targeted cell cycle-promoted factor CCNB1 and suppressed NSCLC cell growth. VPS33B modulated c-Myc/p53/miR-192-3p signaling to target CCNB1 by reducing activation of the Ras/ERK pathway. Our study reveals a novel molecular basis for VPS33B as a tumor suppressor to participate in the pathogenesis of NSCLC.

Identification of candidate biomarkers correlated with poor prognosis of breast cancer based on bioinformatics analysis

“…But, the mechanism of PRC1 in cancer is still unclear. CCNB1 is a regulatory protein involved in mitosis and a critical cell cycle regulator of the G2/M checkpoint [30]. Previous studies have reported that CCNB1 could participate in oncogene pathways among many kinds of cancers, such as BC and colorectal cancer [31][32][33][34].…”

Identification of novel functional CpG-SNPs associated with Type 2 diabetes and birth weight

“…The relationship between VPS33B and T2D is unknown, although VPS33B is expressed in pancreas tissue, and encodes Vascular Protein Sorting-associated protein 33B [ 32 ]. The function of VPS33B refers to intracellular protein trafficking and membrane fusion mechanisms [ 33 ]. It also plays critical roles in bile acids metabolism [ 34 ], which could contribute to the regulation of glucose homeostasis [ 28 ].…”

Unravelling the Role of LncRNA WT1-AS/miR-206/NAMPT Axis as Prognostic Biomarkers in Lung Adenocarcinoma

“…The MYC gene has been confirmed to be a key oncogene affecting many malignant tumors [ 22 ]. Many related studies have reported that MYC plays an important role in the development of LUAD.…”