title: MiR-335 regulates the chemo-radioresistance of small cell lung cancer cells by targeting PARP-1.
abstract: The role of miR-335 in the regulation of chemosensitivity and radiosensitivity of small cell lung cancer (SCLC) was investigated. miR-335 was significantly downregulated in multi-drug-resistant SCLC H69AR and H446DDP cells compared with parental cells as detected by qRT-PCR. Then, we demonstrated the negative correlation between miR-335 expression and the chemo-radiosensitivity of SCLC cells, including cell proliferation, cell clonality and cell apoptosis. In addition, miR-335 overexpression inhibited cell migration in vitro and tumor growth in vivo, whereas inhibition of miR-335 promoted cell migration and tumor growth. The underlying mechanism was further studied. Poly [ADP-ribose] polymerase 1 (PARP-1) was identified as a direct target gene of miR-335 in SCLC by bioinformatics analysis and validated via luciferase reporter assay. Overexpression of miR-335 decreased the expression of PARP-1 mRNA and protein, and NF-κB protein levels were correspondingly downregulated, thus regulating the chemo-radiosensitivity of SCLC. Taken together, these findings indicate that miR-335 may serve as a critical regulator of chemo-radiotherapy resistance in SCLC and a new potential therapeutic target.
authors.affiliation: Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yingshan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Tong
authors.affiliation: Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Meng
authors.affiliation: Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Linlang
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China. Electronic address: 258077534@qq.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Wei
authors.affiliation: Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China. Electronic address: blacktiger@139.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D058990:Molecular Targeted Therapy; D016328:NF-kappa B / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics*; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: C556347:MIRN335 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1
keywords: Multi-drug resistance; NF-κB; PARP-1; Radioresistance; SCLC; miR-335