LncRNA ADAMTS9-AS1, as prognostic marker, promotes cell proliferation and EMT in colorectal cancer

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RESEARCH ARTICLE

LncRNA ADAMTS9‑AS1, as prognostic marker, promotes cell proliferation and EMT in colorectal cancer Wanjing Chen1 · Qian Tu1 · Liang Yu1 · Yanyan Xu1 · Gang Yu1 · Benli Jia1 · Yunsheng Cheng1 · Yong Wang1  Received: 8 April 2020 / Accepted: 4 June 2020 © Japan Human Cell Society 2020

Abstract The long non‐coding RNA antisense 1 ADAMTS9-AS1 has been reported to predict the survival in several tumors, including bladder cancer and breast cancer. However, the clinical significance and biological behaviors of ADAMTS9-AS1 in colorectal cancer (CRC) have not been reported yet. In this study, the expression of ADAMTS9-AS1 was measured in CRC tissues and cell lines using quantitative real-time PCR analysis. The clinical significance of ADAMTS9-AS1 was evaluated with Chi-squared test, Kaplan–Meier method and Cox regression analysis in CRC patients. CCK8 assay, colony formation assay, flow cytometry and transwell assay were used to explore the biological function of ADAMTS9-AS1 knockdown in CRC cell lines (SW1116 and HT29). We further explore the role of ADAMTS9-AS1 in vivo though xenograft tumor assay. Our data showed that ADAMTS9-AS1 expression level was significantly up-regulated in CRC tissues and cell lines compared with corresponding controls. High ADAMTS9-AS1 level was associated with TNM stage, lymph node invasion and worse survival prognosis. Depletion of ADAMTS9-AS1 significantly suppressed cell proliferation, G1/S transition, migration and invasion, as well as suppressed CDK4/Cyclin D1 and epithelial–mesenchymal transition (EMT). To sum up, these findings illustrated that ADAMTS9-AS1 might be a promising therapeutic target and prognostic factor for CRC. Keywords  CRC​ · ADAMTS9-AS1 · Prognosis · Proliferation · G1/S transition · EMT Abbreviations CRC​ Colorectal cancer lncRNAs Long non-coding RNAs EMT Epithelial to mesenchymal transition DMEM Dulbecco’s modified Eagle’s medium FBS Fetal bovine serum NC Negative control CCK-8 Cell Counting Kit-8 PVDF Polyvinylidene fluoride

Wanjing Chen and Qian Tu contributed equally to this work. * Yunsheng Cheng [email protected] * Yong Wang [email protected] 1



Department of General Surgery, Economic and Technological Development District, The Second Hospital of Anhui Medical University, No.678 Furong Road, Hefei, Anhui, China

Introduction Colorectal cancer (CRC) as a common human malignancy in digestive system ranks the leading cause of tumor-related deaths worldwide according to the latest cancer statistics data [1]. Currently, substantial progresses have been made in conventional treatments, including resection, radiation therapy, and chemotherapy, but the existence of tumor metastasis remains the leading cause of unfavorable survival prognosis [2–4]. Therefore, the identification of genes associated with CRC metastasis is of great importance to develop effective treatments and improve clinical outcomes. Long non-coding RNAs (LncRNAs) are a novel group of RNA transcripts with more than 200 nucleotides in length, which participates in