NCBP1 promotes the development of lung adenocarcinoma through up‐regulation of CUL4B

Abstract

Lung cancer is the most frequent cancer type and is the leading cause of tumour‐associated deaths worldwide. Nuclear cap‐binding protein 1 (NCBP1) is necessary for capped RNA processing and intracellular localization. It has been reported that silencing of NCBP1 resulted in cell growth reduction in HeLa cells. Nevertheless, its clinical significance and underlying molecular mechanisms in non–small‐cell lung cancer remain unclear. In this study, we found that NCBP1 was significantly overexpressed in lung cancer tissues and several lung cancer cell lines. Through knockdown and overexpression experiments, we showed that NCBP1 promoted lung cancer cell growth, wound healing ability, migration and epithelial‐mesenchymal transition. Mechanistically, we found that cullin 4B (CUL4B) was a downstream target gene of NCBP1 in NSCLC. NCBP1 up‐regulated CUL4B expression via interaction with nuclear cap‐binding protein 3 (NCBP3). CUL4B silencing significantly reversed NCBP1‐induced tumorigenesis in vitro. Based on these findings, we propose a model involving the NCBP1‐NCBP3‐CUL4B oncoprotein axis, providing novel insight into how CUL4B is activated and contributes to LUAD progression.

Assessment of Genetic Susceptibility to Multiple Primary Cancers through Whole-Exome Sequencing in Two Large Multi-Ancestry Studies

“…Regarding rs143745791, germline variants in NCBP1 have not been previously associated with cancer; because it is rare (MAF < 0.2%), larger sequencing efforts may be necessary identify variation in studies of individuals with a single cancer. Expression of this gene has been found to promote lung cancer growth and poor prognosis 42 , and NCBP1 is overexpressed in basal-like and triple-negative breast cancers 43 . Similarly, BRCA1/2 germline variants are prevalent among these subtypes; however, in our study populations, BRCA1/2 carriers were more common among those with an additional ovarian cancer whereas NCBP1 carriers more frequently had an additional cervical cancer.…”

“…Regarding rs143745791, germline variants in NCBP1 have not been previously associated with cancer; because it is rare (MAF < 0.2%), larger sequencing efforts may be necessary identify variation in studies of individuals with a single cancer. Expression of this gene has been found to promote lung cancer growth and poor prognosis 42 , and NCBP1 is overexpressed in basal-like and triple-negative breast cancers 43 .…”

Circ_0015756 promotes the progression of ovarian cancer by regulating miR-942-5p/CUL4B pathway

“…CUL4B is dysregulated in various tumors and participates in many cellular processes related to tumors [ 28 ]. CUL4B functions as a carcinogen in diverse tumors, including bladder cancer [ 29 ], colorectal cancer [ 30 ] and lung adenocarcinoma [ 31 ]. In ovarian cancer, CUL4B was overtly up-regulated in cancer tissues and CUL4B facilitated cancer cell proliferation by mediating CDK2 and CyclinD1 [ 32 ].…”

The Cap-Binding Complex CBC and the Eukaryotic Translation Factor eIF4E: Co-Conspirators in Cap-Dependent RNA Maturation and Translation

“…The depletion of NCBP2 or NCBP1 is not lethal in mammalian cells [ 6 ]. However, a recent study pointed out a critical role in oncogenic processes such as cell proliferation, invasion, and migration [ 183 ]. NCBP1 is elevated in lung adenocarcinoma and a mechanism associating NCPB1 to NCBP3 increased the expression of CUL4B, leading to oncogenic phenotypes in this context [ 183 ].…”

“…However, a recent study pointed out a critical role in oncogenic processes such as cell proliferation, invasion, and migration [ 183 ]. NCBP1 is elevated in lung adenocarcinoma and a mechanism associating NCPB1 to NCBP3 increased the expression of CUL4B, leading to oncogenic phenotypes in this context [ 183 ]. The protein atlas also identified NCBP1 ( (access on 25 November 2021)) as a favorable prognostic marker for prostate cancer and unfavorable for pancreatic cancer, while NCBP2 ( (access on 25 November 2021)) has been identified as an unfavorable prognostic marker for liver, pancreatic, and prostate cancer.…”