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MicroRNA-497 inhibits tumor growth and increases chemosensitivity to 5-fluorouracil treatment by targeting KSR1

2015; Impact Journals LLC; Volume: 7; Issue: 3 Linguagem: Inglês

10.18632/oncotarget.6545

1949-2553

Lin Wang, Chengfei Jiang, Dongmei Li, Xin Ge, Zhumei Shi, Chong-yong Li, Xue Liu, Yu Yin, Linlin Zhen, Liu L, Bing‐Hua Jiang,

MXene and MAX Phase Materials

// Lin Wang 1, * , Cheng-fei Jiang 1, * , Dong-mei Li 1, 3, * , Xin Ge 1 , Zhu-mei Shi 1, 4 , Chong-yong Li 1 , Xue Liu 1 , Yu Yin 1, 5 , Linlin Zhen 2 , Ling-Zhi Liu 6 , Bing-Hua Jiang 1, 6 1 State Key Lab of Reproductive Medicine, Collaborative Innovation Center for Cancer Personalized Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China 2 Department of Breast and Thyroid Surgery, Huai'an First People's Hospital, Huai'an, Jiangsu, China 3 Ninggao Personalized Medicine and Technology Innovation Center, Nanjing, China 4 Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China 5 Department of Pathology, Anhui Medical University, Hefei, China 6 Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA * These authors have contributed equally to this work Correspondence to: Bing-Hua Jiang, e-mail: binghjiang@yahoo.com Linlin Zhen, e-mail: simu1027@sina.com Keywords: miR-497, colorectal cancer, KSR1, tumorigenesis, chemosensitivity Received: July 28, 2015 Accepted: November 16, 2015 Published: December 09, 2015 ABSTRACT Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Recently, downregulation of microRNA-497 (miR-497) has been observed in CRC tissues. In this study, we found that miR-497 expression levels were downregulated in human CRC specimens compared to the adjacent normal tissues. MiR-497 expression levels were strongly correlated with clinical stages and lymph node metastases. Furthermore, kinase suppressor of ras 1 (KSR1), a known oncogene, was a direct target of miR-497, and KSR1 expression levels were inversely correlated with miR-497 expression levels in human CRC specimens. Overexpression of miR-497 inhibited cell proliferation, migration, invasion and increased chemosensitivity to 5-fluorouracil treatment, whereas forced expression of KSR1 had the opposite effect. Taken together, these results revealed that lower miR-497 levels in human CRC tissues induce KSR1 expression which is associated with CRC cancer occurrence, advanced stages, metastasis and chemoresistance. Lower miR-497 levels may be a potential biomarker for CRC advanced stages and treatment response.