title: Long noncoding RNA-HOTAIR affects chemoresistance by regulating HOXA1 methylation in small cell lung cancer cells.
abstract: Homeobox (HOX) transcript antisense RNA (HOTAIR), a long intergenic noncoding RNA (lincRNA), has been reported to play an oncogenic role in various cancers including small cell lung cancer (SCLC). However, it is not known whether HOTAIR can modulate chemoresistance in SCLC. The aim of this study is to investigate the roles of HOTAIR in chemoresistance of SCLC and its possible molecular mechanism. Knockdown of HOTAIR was carried out in SCLC multidrug-resistant cell lines (H69AR and H446AR) and the parental cell lines (H69 and H446) to assess its influence on chemoresistance. The results showed that downregulation of HOTAIR increased cell sensitivity to anticancer drugs through increasing cell apoptosis and cell cycle arrest, and suppressed tumor growth in vivo. Moreover, HOXA1 methylation increased in the resistant cells using bisulfite sequencing PCR. Depletion of HOTAIR reduced HOXA1 methylation by decreasing DNMT1 and DNMT3b expression. The interaction between HOTAIR and HOXA1 was validated by RNA immunoprecipitation. Taken together, our study suggested that HOTAIR mediates chemoresistance of SCLC by regulating HOXA1 methylation and could be utilized as a potential target for new adjuvant therapies against chemoresistance.
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Fang
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.|Department of Pathology, Guangdong Provincial Maternity and Child Care Center, Guangzhou, China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Tong
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Ruixiang
authors.initials: R
authors.lastname: Tang
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Linlang
authors.initials: L
authors.lastname: Guo
mesh_terms: D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D055752:Small Cell Lung Carcinoma / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099261:Homeobox A1 Protein
chemical_list: D018398:Homeodomain Proteins; D062085:RNA, Long Noncoding; D014157:Transcription Factors; D000099261:Homeobox A1 Protein