Long noncoding RNA Linc00337 functions as an E2F1 co-activator and promotes cell proliferation in pancreatic ductal aden
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(2020) 39:216
RESEARCH
Open Access
Long noncoding RNA Linc00337 functions as an E2F1 co-activator and promotes cell proliferation in pancreatic ductal adenocarcinoma Huakai Wang1†, Shiyong Yu1†, Huan Peng1, Yijun Shu1, Wenjie Zhang2, Qi Zhu1, Yingxia Wu1, Yijun Xu1, Jiqi Yan3* and Honggang Xiang1*
Abstract Background: Long noncoding RNA (lncRNA) Linc00337 has been implicated in lung, gastric, colorectal and esophageal squamous cell carcinoma progression via various mechanisms; however, its clinicopathological significance and role in pancreatic ductal adenocarcinoma (PDAC) progression remains largely unknown. Methods: Multiple approaches such as bioinformatic analysis, Transfection, quantitative real-time-PCR, Western blotting, animal studies, RNA-immunoprecipitation (RIP), RNA-pulldown and RNA-Fluorescence in situ hybridization (RNA-FISH) and were utilized to explore the role of Linc00337 in PDAC. Results: Here we identified Linc00337 is an oncogenic lncRNA during PDAC progression. We found that the expression of Linc00337 is elevated in PDAC tissues and the higher Linc00337 predicts dismal prognosis. Functionally, Linc00337 promotes PDAC cell proliferation and cell cycle transition both in vitro and in vivo. Mechanistically, Linc00337 binds to E2F1 and functions as an E2F1 coactivator to trigger the targets expression during PDAC progression. Conclusion: Our results demonstrate a reciprocal regulation mechanism between Linc00337 and E2F1 in PDAC progression and report the clinical value of Linc00337 for PDAC prognosis and treatment. Keywords: PDAC, Long noncoding RNA, Linc00337, E2F1, Cell cycle, Cell proliferation
Background Pancreatic ductal adenocarcinoma (PDAC) accounts for approximately 90% of all pancreatic carcinomas [1] and has a poor five-year survival rate of 2–9% [2] owing to a lack of early symptoms and early detection and most cases being diagnosed at an advanced stage. PDAC * Correspondence: [email protected]; [email protected] † Huakai Wang and Shiyong Yu contributed equally to this work. 3 Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China 1 Department of General Surgery Pudong New Area People’s Hospital Pudong New Area, No. 490, South Chuanhuan Road, Shanghai 201200, China Full list of author information is available at the end of the article
tumorigenesis and progression are the result of a series of gene mutations and previous studies have revealed that KRAS, P16, CDNK27, P53, and SMAD4 mutations contribute toward PDAC development [3, 4]; however, the detailed molecular pathogenesis of PDAC remains largely unknown. Cell cycle deregulation is a common feature of human cancer [5], with fundamental mutations in the genetic control of cell division resulting in spontaneous proliferation [6]. For instance, P16 and P53 mutations release the inhibition of CDK4/CDK6-mediated RB phosphorylation and trigger E2F activation-mediated cell cycle
© The Author(s). 2020 Open Access This article is licensed under a Creative Com
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