title: Lin28A enhances chemosensitivity of colon cancer cells to 5-FU by promoting apoptosis in a let-7 independent manner.
abstract: RNA-binding protein Lin28A is frequently over-expressed in human malignant tumors and is associated with tumor advance and poor prognosis. However, the expression pattern and functions of Lin28A in colon cancer are unknown. In this study, we detected the expression of Lin28A in colon cancer patients and tested the effect of Lin28A on the chemotherapeutic sensitivity of colon cancer cells to 5-fluorouracil (5-FU). As expected, we showed that Lin28A is up-regulated in 73.3 % of colon cancer patients. However, to our surprise, we found that oncogenic protein Lin28A-enforced expression in colon cancer cells enhanced the chemosensitivity of cancer cells to 5-FU via promoting the cell apoptosis. Further mechanisms study revealed that the effect of Lin28A increasing chemosensitivity of cancer cells is in a let-7 independent manner, but which is associated with decreasing the expression of DNA damage repair protein H2AX. Conclusively, here we reported an unexpected function of Lin28A, which may shed lights on fully understanding the physiological and pathological roles of this oncogene.
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin, China.
authors.forename: Tianzhen
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Han
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Gastrointestinal Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: Ci
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Gastrointestinal Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Breast Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shan
authors.affiliation: Department of Gastrointestinal Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin, China.
authors.forename: Mingjiao
authors.initials: M
authors.lastname: Weng
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Yunwei
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Colorectal Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China. 13351112888@163.com.
authors.forename: BinBin
authors.initials: B
authors.lastname: Cui
authors.affiliation: Department of Medical Genetics, Medical College, Henan University of Science and Technology, Luoyang, China. shenba433@163.com.
authors.forename: Guomin
authors.initials: G
authors.lastname: Shen
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin, China. lixiaobo@ems.hrbmu.edu.cn.
authors.forename: Xiaobo
authors.identifier: http://orcid.org/0000-0003-1037-3903
authors.initials: X
authors.lastname: Li
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004260:DNA Repair / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D045325:HCT116 Cells; D006657:Histones / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000502:physiology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012334:RNA, Neoplasm / Q000502:physiology; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D016037:Single-Blind Method
chemical_list: D000964:Antimetabolites, Antineoplastic; C468783:H2AX protein, human; D006657:Histones; C516326:LIN28B protein, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; C487931:mirnlet7 microRNA, human; D005472:Fluorouracil
keywords: Apoptosis; Chemosensitivity; Colon cancer; H2AX; Lin28A