Downregulation of KIAA1199 by miR‐486‐5p suppresses tumorigenesis in lung cancer. (9th June 2020)

• Record Type: Journal Article
• Authors: Wang, Anqi; Zhu, Jianjie; Li, Juan; Du, Wenwen; Zhang, Yang; Cai, Tingting; Liu, Ting; Fu, Yulong; Zeng, Yuanyuan; Liu, Zeyi; Huang, Jian‐an
• Is Part Of: Cancer medicine. Volume 9:Number 15(2020)
• Page Start: 5570
• Page End: 5586
• Publication Date: 2020-06-09
• Subjects: cell motility -- cell proliferation -- KIAA1199 -- microRNA -- miR‐486‐5p -- Non‐small cell lung cancer (NSCLC); 616.994005
• DOI: 10.1002/cam4.3210
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: Lung cancer is the primary cause of death among cancer patients in China, among which nonsmall cell lung cancer (NSCLC) makes up the great majority. Hence, it is imperative to identify the biomarkers and mechanisms involved in NSCLC oncogenesis. Our present research found that KIAA1199 expression was significantly increased in NSCLC and closely related to cell proliferation, motility, and poor prognosis. We demonstrated that knockdown of KIAA1199 reduced NSCLC cell growth and motility in vitro whereas overexpression of KIAA1199 had the opposite effect. Inhibition of KIAA1199 significantly suppressed tumor growth in mouse NSCLC xenograft models. Mechanistically, as an epidermal growth factor receptor (EGFR)‐binding protein, KIAA1199 promotes EGFR signaling and regulates EGFR‐dependent Src, Erk, and Akt phosphorylation, as well as downstream kinases in the EGF‐mediated EMT pathway. We demonstrated that KIAA1199 can function as a direct binding target for miR‐486‐5p and that miR‐486‐5p overexpression can attenuate proliferation and migration of NSCLC cells via regulating the EGFR signaling pathways. To conclude, our results defined KIAA1199 as an oncogenic protein that promotes cancer cell proliferation and migration by regulating EGF‐mediated signaling pathways. This study provided new insight into NSCLC oncogenesis, which could lead to the development of innovative therapeutic plans for NSCLC. Abstract : In this study, we defined KIAA1199 as an oncogenic protein whose expression is markedly higher in lung cancer tissues and is regulated by miR‐486‐5p. KIAA1199 promotes cancer cell proliferation and migration by regulating EGFR‐mediated signaling pathways. These findings may lead to the development of novel therapeutic strategies for NSCLC.