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  • br Conclusion The hub gene

    2022-05-17


    Conclusion The hub gene KIBRA and the Hippo signaling pathway were downregulated and miR-21 was upregulated in LAD. MiR-21 promoted the viability and mobility of LAD cells, reduced apoptosis and suppressed the Hippo signaling pathway in LAD through targeting KIBRA.
    Funding The study was approved by the Basic and Frontier Project of Henan Provincial Science and Technology Department: Expression of sodium salt growth factor and receptor in pulmonary fibrosis (Grant Number: 142300410383).
    Declarations of interest
    Acknowledgements
    Introduction Colorectal cancer (CRC) is the most common gastrointestinal tumor, accounting for an estimated 1.3 million cancer-related deaths annually worldwide. Despite substantial advances in systemic or individual treatment, the prognosis remains bleak due to late detection and diagnosis at an advanced stage of CRC. Therefore, the identification of novel and suitable biomarkers for early detection in CRC may significantly facilitate to improve the number of CRC-associated deaths. ZNF280A, first identified through an integrative high-resolution whole-genome profiling in mantle cell lymphoma, is a member of the zinc-finger protein family, carrying a unique zinc-finger motif composed of two contiguous Cys2His2-type fingers. This Cys2His2-like fold group (C2H2) is by far the best-characterized class of zinc fingers, and it is extremely common in mammalian transcription factors. Although functioning in diverse biological roles by binding DNA or RNA and mediating protein-protein interactions, this class of zinc fingers is best known for its role in sequence-specific DNA-binding proteins via its typical tandem repeats, with two or more fingers comprising the DNA-binding domain of the protein that occupies the major groove of DNA. Numerous studies have demonstrated that different members of the zinc-finger proteins, such as ZEB2, ZNF746, PISA, and Snail1, have been reported to be involved in the development, progression, and metastasis of CRC,5, 6, 7, 8 indicating that zinc-finger proteins may play an important role in CRC. Compared with these well-documented zinc-finger proteins members, reports on the biological function and role of ZNF280A in cancers are scanty. The Hippo-signaling pathway has been found to be frequently inactivated in multiple human cancer types.9, 10, 11 The Hippo pathway mainly consists of four core kinase cassette components, including the adaptor proteins SAV1 and MOB1 and kinases MST1/2 and LATS1/2. The Hippo signaling is active via tightly controlling the activity of Yes Associated Protein (YAP) and Tafazzin (TAZ) through phosphorylation-ubiquitination mechanisms.12, 13 While Hippo signaling is absent, unphosphorylated YAP1 and/or TAZ translocates to the nucleus of cells, promoting the transcriptional activity of TEA domain (TEAD) family members (TEAD1–TEAD4) as the transcriptional co-activators via transcriptionally upregulating multiple downstream effectors to exert a pleiotropic role in the progression and metastasis of cancers.14, 15, 16 Several lines of evidence have shown that the inactivation of Hippo signaling was implicated in various processes of CRC. For example, REGγ contributed to the growth of CRC cells via directly interacting with LATS1, leading to the degradation of LATS1 and inactivation of Hippo signaling; in addition, SCC-S2 overexpression was found to promote the invasion and metastasis of CRC via depressing Hippo signaling. Our previous study demonstrated that the inactivation of Hippo signaling by the overexpression of TFAP2C promoted the progression of CRC via maintaining cancer stem cell-like phenotypes. Thus, these studies support the notion that the inactivation of Hippo pathway plays a crucial role in the progression and metastasis of CRC. In this study, our findings revealed for the first time that ZNF280A was dramatically upregulated in CRC tissues, which significantly correlated with advanced clinicopathological features and poor overall and progression-free survival in CRC patients. Loss-of-function experiments demonstrated that silencing ZNF280A attenuated the proliferation and retarded cell cycle progression in CRC cells in vitro and repressed the tumorigenesis of CRC cells in vivo. Mechanistic investigation further showed that silencing ZNF280A activated Hippo signaling via upregulating phophorylated MST1/2 and LATS1 expression and downregulating TAZ and YAP expression in CRC cells. Therefore, our findings indicate that ZNF280A holds promise to serve as a novel marker for early detection and diagnosis in CRC patients.