title: MicroRNA-497 inhibits tumor growth and increases chemosensitivity to 5-fluorouracil treatment by targeting KSR1.
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.
authors.affiliation: State Key Lab of Reproductive Medicine, Collaborative Innovation Center for Cancer Personalized Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Lab of Reproductive Medicine, Collaborative Innovation Center for Cancer Personalized Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.
authors.forename: Cheng-fei
authors.initials: CF
authors.lastname: Jiang
authors.affiliation: State Key Lab of Reproductive Medicine, Collaborative Innovation Center for Cancer Personalized Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.|Ninggao Personalized Medicine and Technology Innovation Center, Nanjing, China.
authors.forename: Dong-mei
authors.initials: DM
authors.lastname: Li
authors.affiliation: State Key Lab of Reproductive Medicine, Collaborative Innovation Center for Cancer Personalized Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ge
authors.affiliation: State Key Lab of Reproductive Medicine, Collaborative Innovation Center for Cancer Personalized Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.|Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Zhu-mei
authors.initials: ZM
authors.lastname: Shi
authors.affiliation: State Key Lab of Reproductive Medicine, Collaborative Innovation Center for Cancer Personalized Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.
authors.forename: Chong-yong
authors.initials: CY
authors.lastname: Li
authors.affiliation: State Key Lab of Reproductive Medicine, Collaborative Innovation Center for Cancer Personalized Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Lab of Reproductive Medicine, Collaborative Innovation Center for Cancer Personalized Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.|Department of Pathology, Anhui Medical University, Hefei, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Breast and Thyroid Surgery, Huai'an First People's Hospital, Huai'an, Jiangsu, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Zhen
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Liu
authors.affiliation: State Key Lab of Reproductive Medicine, Collaborative Innovation Center for Cancer Personalized Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.|Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Bing-Hua
authors.initials: BH
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D011494:Protein Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000964:Antimetabolites, Antineoplastic; C559640:MIRN497 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D011494:Protein Kinases; C097199:KSR-1 protein kinase; D005472:Fluorouracil
keywords: KSR1; chemosensitivity; colorectal cancer; miR-497; tumorigenesis