title: Overexpression of secretagogin inhibits cell apoptosis and induces chemoresistance in small cell lung cancer under the regulation of miR-494.
abstract: Secretagogin (SCGN) has recently been identified to play a crucial role in cell apoptosis, receptor signaling and differentiation. However, its clinical significance and functional roles in SCLC chemoresistance remain unknown. Here we examined the expression of SCGN in clinical samples from SCLC patients and evaluated its relation with clinical prognosis. Then up and down-regulation of SCGN were carried out in SCLC cell lines to assess its influence on chemoresistance. Furthermore, luciferase reporter assay was used to evaluate whether SCGN is a novel direct target of miR-494. Our results revealed that elevated expression of SCGN was correlated with the poorer prognosis of SCLC patients and the more significant correlation with chemosensitivity. We also found that knockdown of SCGN expression in H69AR and H446AR cells increased chemosensitivity via increasing cell apoptosis and cell cycle arrest of G0/G1 phase, while over-expression of SCGN reduced chemosensitivity in sensitive H69 and H446 cells. SCGN as a novel target of miR-494 by luciferase reporter assay, up-regulation of miR-494 can sensitize H69AR cells to chemotherapeutic drugs. These results suggest SCGN is involved in the chemoresistance of SCLC under the regulation of miR-494 and may be a potential biomarker for predicting therapeutic response in treatment SCLC.
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China. Department of Oncology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China. Contributed equally to this work.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China. Department of Pathology, School of Basic Medicine Science, Guangdong Medical College, Dongguan, China. Contributed equally to this work.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China. Department of Pathology, the Third Affiliated Hospital Of Guangzhou Medical University, Guangzhou, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Hongzhan
authors.initials: H
authors.lastname: Liao
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China. Department of Pathology, Guangdong Women and Children Hospital, Guangzhou, China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Organ Transplantation, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Linlang
authors.initials: L
authors.lastname: Guo
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064046:Secretagogins / Q000096:biosynthesis*; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: C547168:MIRN494 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; C576556:SCGN protein, human; D064046:Secretagogins