LncRNA HAND2-AS1 inhibits 5-fluorouracil resistance by modulating miR-20a/PDCD4 axis in colorectal cancer |
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| Institution: | 1. Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China;2. Department of Anal-Colorectal Surgery, General Hospital of Ningxia Medical University, Yinchuan 750004, China;3. Department of Critical Care Medicine, Henan Provincial People’s Hospital, Zhengzhou 450003, China;4. Department of Pathology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China;5. Department of Pharmacy, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China;1. Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China;2. First Clinical Medical College of Nanjing Medical University, Nanjin, Jiangsu Province, China;3. Department of Gastroenterology, Affiliated Zhongshan Hospital of fudan university, Shanghai, China;4. Institute for Disaster Management and Reconstruction, Sichuan University-The Hong Kong Polytechnic University, Chengdu, Sichuan Province, China;5. Epidemiology of Functioning, Swiss Paraplegic Research, Nottwil, Switzerland;6. Department of Gastroenterology, Sir Run Run Hospital Affiliated with Nanjing Medical University, Nanjing, Jiangsu Province, China;1. The Fifth Department of Digestion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China;2. Department of Digestion, Huaihe Hospital of Henan University, Kaifeng, 475000, China;1. Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi''an Jiaotong University Health Science Center, Xi''an, China;2. Department of General Surgery, The Second Affiliated Hospital of Xi''an Jiaotong University, Xi''an, China;3. Medical College, Yan''an University, Yan''an, China;4. Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi''an Jiaotong University, Xi''an, China |
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| Abstract: | BackgroundChemoresistance is one of the main obstacles in the therapy of human cancers, including colorectal cancer (CRC). Long non-coding RNA heart and neural crest derivatives expressed 2-antisense RNA 1 (lncRNA HAND2-AS1) has been demonstrated to be associated with CRC. However, the function of HAND2-AS1 in 5-Fluorouracil (5-FU) resistance of CRC remains unclear.MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of HAND2-AS1, miR-20a and programmed cell death factor 4 (PDCD4) mRNA. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was conducted to evaluate IC50 of 5-FU and cell proliferation. Flow cytometry analysis was used to determine cell apoptosis. Transwell assay was carried out to measure cell migration and invasion. Western blot assay was conducted to examine the protein levels of B-cell lymphoma-2 (Bcl-2), BCL2-Associated X (Bax), matrix metalloprotein 2 (MMP2), MMP9 and PDCD4. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down assay were utilized to verify the combination between miR-20a and HAND2-AS1. Dual-luciferase reporter assay was used to analyze the association between miR-20a and PDCD4. Murine xenograft assay was used to confirm the function of HAND2-AS1 in vivo.ResultsHAND2-AS1 and PDCD4 were downregulated and miR-20a was upregulated in 5-FU-resistant CRC tissues and cells. HAND2-AS1 suppressed 5-FU resistance, cell proliferation, migration and invasion and promoted cell apoptosis in 5-FU-resistant CRC cells. HAND2-AS1 acted as a sponge of miR-20a to regulate PDCD4 expression. Moreover, HAND2-AS1 suppressed cell progression and 5-FU resistance by upregulating PDCD4 via sponging miR-20a in 5-FU-resistant CRC cells. Besides, HAND2-AS1 inhibited tumor growth in vivo.ConclusionHAND2-AS1/miR-20a/PDCD4 axis inhibited cell progression and 5-FU resistance in 5-FU-resistant CRC cells. |
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