title: Tetracycline-inducible shRNA targeting antisense long non-coding RNA HIF1A-AS2 represses the malignant phenotypes of bladder cancer.
abstract: Various studies have indicated that long non-coding RNAs (lncRNAs) play vital roles in the cancer development and progression. LncRNA hypoxia inducible factor 1alpha antisense RNA-2 (HIF1A-AS2) is upregulated in gastric carcinomas and knockdown of HIF1A-AS2 expression by siRNA could inhibit cell proliferation in vitro and tumorigenesis in vivo. Inspired by these observations, we hypothesized that HIF1A-AS2 possibly plays the analogous roles in bladder cancer. In our study, we first reported that HIF1A-AS2 was up-regulated in bladder cancer tissues and cells, and HIF1A-AS2 expression level in bladder cancer tissues is positively associated with advanced clinical pathologic grade and TNM phase. Cell proliferation inhibition, cell migration suppression and apoptosis induction were observed by silencing HIF1A-AS2 in bladder cancer T24 and 5637 cells. Overexpression of HIF1A-AS2 in SV-HUC-1 cells could promote cell proliferation, cell migration and anti-apoptosis. Besides, we utilized the emerging technology of medical synthetic biology to design tetracycline-inducible small hairpin RNA (shRNA) vector which specifically silenced HIF1A-AS2 in a dosage-dependent manner to inhibit the progression of human bladder cancer. In conclusion, our data suggested that HIF1A-AS2 plays oncogenic roles and can be used as a therapeutic target for treating human bladder cancer. Synthetic "tetracycline-on" switch system that quantitatively controlled the expression of HIF1A-AS2 in bladder cancer can inhibit the progression of bladder cancer cells in a dosage-dependent manner. Our findings provide new insights into the role of the lncRNA HIF1A-AS2 in the bladder cancer.
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, Clinical Institute of Anhui Medical University, The First Affiliated Hospital of Shenzhen University, Shenzhen 518039, Guangdong Province, China; Department of Urology, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu 322000, Zhejiang Province, China; Anhui Medical University, Hefei 230032, Anhui Province, China.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Chen
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, Clinical Institute of Anhui Medical University, The First Affiliated Hospital of Shenzhen University, Shenzhen 518039, Guangdong Province, China; Shantou University Medical College, Shantou 515041, Guangdong Province, China.
authors.forename: Chengle
authors.initials: C
authors.lastname: Zhuang
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, Clinical Institute of Anhui Medical University, The First Affiliated Hospital of Shenzhen University, Shenzhen 518039, Guangdong Province, China.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, Clinical Institute of Anhui Medical University, The First Affiliated Hospital of Shenzhen University, Shenzhen 518039, Guangdong Province, China; Shantou University Medical College, Shantou 515041, Guangdong Province, China.
authors.forename: Jianfa
authors.initials: J
authors.lastname: Li
authors.affiliation: Anhui Medical University, Hefei 230032, Anhui Province, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Dai
authors.affiliation: Department of Urology, The Third Affiliated Hospital of Southen Medical University, Guangzhou 510630, Guangdong Province, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xia
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, Clinical Institute of Anhui Medical University, The First Affiliated Hospital of Shenzhen University, Shenzhen 518039, Guangdong Province, China; Shantou University Medical College, Shantou 515041, Guangdong Province, China.
authors.forename: Yonghao
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, Clinical Institute of Anhui Medical University, The First Affiliated Hospital of Shenzhen University, Shenzhen 518039, Guangdong Province, China; Shantou University Medical College, Shantou 515041, Guangdong Province, China.
authors.forename: Junhao
authors.initials: J
authors.lastname: Lin
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, Clinical Institute of Anhui Medical University, The First Affiliated Hospital of Shenzhen University, Shenzhen 518039, Guangdong Province, China; Shantou University Medical College, Shantou 515041, Guangdong Province, China.
authors.forename: Zhicong
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, Clinical Institute of Anhui Medical University, The First Affiliated Hospital of Shenzhen University, Shenzhen 518039, Guangdong Province, China; Anhui Medical University, Hefei 230032, Anhui Province, China.
authors.forename: Anbang
authors.initials: A
authors.lastname: He
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, Clinical Institute of Anhui Medical University, The First Affiliated Hospital of Shenzhen University, Shenzhen 518039, Guangdong Province, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Xu
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, Clinical Institute of Anhui Medical University, The First Affiliated Hospital of Shenzhen University, Shenzhen 518039, Guangdong Province, China; Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai 200000, China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, Beijing 100034, China.
authors.forename: Yinglu
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, Clinical Institute of Anhui Medical University, The First Affiliated Hospital of Shenzhen University, Shenzhen 518039, Guangdong Province, China; Anhui Medical University, Hefei 230032, Anhui Province, China; Shantou University Medical College, Shantou 515041, Guangdong Province, China; Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, Beijing 100034, China. Electronic address: caizhiming2000@163.com.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, Clinical Institute of Anhui Medical University, The First Affiliated Hospital of Shenzhen University, Shenzhen 518039, Guangdong Province, China; Anhui Medical University, Hefei 230032, Anhui Province, China; Shantou University Medical College, Shantou 515041, Guangdong Province, China; Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, National Urological Cancer Center, Beijing 100034, China. Electronic address: pony8980@163.com.
authors.forename: Weiren
authors.initials: W
authors.lastname: Huang
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010641:Phenotype; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000235:genetics*; D000067492:RNAi Therapeutics / Q000379:methods*; D013752:Tetracycline / Q000494:pharmacology*; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; C000614114:long noncoding RNA HIF1A-AS2, human; D013752:Tetracycline
keywords: Bladder cancer; HIF1A-AS2; LncRNAs; Synthetic biology; Tetracycline-inducible