Circular RNA circ-TNPO3 inhibits clear cell renal cell carcinoma metastasis by binding to IGF2BP2 and destabilizing SERPINH1 mRNA

作者全名："Pan, Xiaojuan; Huang, Bo; Ma, Qiang; Ren, Junwu; Liu, Yuying; Wang, Cong; Zhang, Dawei; Fu, Jian; Ran, Lingyu; Yu, Ting; Li, Haiping; Wang, Xiaolin; Yang, Feifei; Liang, Ce; Zhang, Yuying; Wang, Shimin; Ren, Jingjing; Li, Wei; Wang, Yongquan; Bin Xiao"

作者地址："[Pan, Xiaojuan; Huang, Bo; Ma, Qiang; Ren, Junwu; Liu, Yuying; Li, Haiping; Wang, Xiaolin; Yang, Feifei; Liang, Ce; Zhang, Yuying; Wang, Shimin; Bin Xiao] Chongqing Med Univ, Coll Pharm, Chongqing, Peoples R China; [Wang, Cong; Zhang, Dawei; Fu, Jian; Wang, Yongquan] Army Med Univ, Southwest Hosp, Dept Urol, Chongqing 400038, Peoples R China; [Ran, Lingyu] Army Med Univ, Southwest Hosp, Dept Kidney, Chongqing, Peoples R China; [Yu, Ting; Ren, Jingjing] Peoples Liberat Army, Dept Clin Lab, Hosp 89, Weifang, Peoples R China; [Li, Wei] Army Med Univ, South West Hosp, Dept Pharm, Chongqing 400038, Peoples R China"

通信作者："Bin X (通讯作者)，Chongqing Med Univ, Coll Pharm, Chongqing, Peoples R China.; Wang, YQ (通讯作者)，Army Med Univ, Southwest Hosp, Dept Urol, Chongqing 400038, Peoples R China.; Li, W (通讯作者)，Army Med Univ, South West Hosp, Dept Pharm, Chongqing 400038, Peoples R China."

来源：CLINICAL AND TRANSLATIONAL MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000829354500001

JCR分区：Q1

影响因子：10.6

年份：2022

卷号：12

期号：7

开始页：　

结束页：　

文献类型：Article

关键词：circ-TNPO3; clear cell renal cell carcinoma; IGF2BP2; SERPINH1

摘要："Background Clear cell renal cell carcinoma (ccRCC) is a common malignant tumour of the urinary tract. The major causes of poor prognosis are the lack of early diagnosis and metastasis. Accumulating research reveals that circular RNAs (circRNAs) can play key roles in the development and the progression of cancer. However, the role of circRNAs in ccRCC is still uncertain. Methods The circRNAs microarray (n = 4) was performed to investigate the circRNAs with differential expression in ccRCC tissues. The candidate circRNA was selected based on the cut-off criteria, such as circRNA expression abundance, circRNA size and the design of divergent primers. The circ-transportin-3 (TNPO3) levels in ccRCC tissues were tested by quantitative real-time (qRT)-PCR (n = 110). The characteristics and subcellular localization of circ-TNPO3 were identified via RNase R assay, qRT-PCR and fluorescence in situ hybridization (FISH). Then, we explored the biological roles of circ-TNPO3 in ccRCC via the function experiments in vitro and in vivo. RNA pull-down, RNA immunoprecipitation, bioinformatic analysis, RNA-FISH assays and rescue assays were applied to validate the interactions between circ-TNPO3, insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) and serpin family H member 1 (SERPINH1) to uncover the underlying molecular mechanisms of circ-TNPO3. Results We detected the obvious downregulation of circ-TNPO3 in ccRCC compared to matched adjacent normal tissues (n = 110). The lower circ-TNPO3 expression was found in ccRCC patients with distant metastasis, higher World Health Organization/International Society of Urologic Pathologists (WHO/ISUP) grade and more advanced tumour T stage. In vitro and in vivo, circ-TNPO3 significantly suppressed the proliferation and migration of ccRCC cells. Mechanistically, we elucidated that circ-TNPO3 directly bound to IGF2BP2 protein and then destabilized SERPINH1 mRNA. Moreover, IGF2BP2/SERPINH1 axis was responsible for circ-TNPO3's function of inhibiting ccRCC metastasis. Epithelial splicing regulatory protein 1 (ESRP1) was probably involved in the biogenesis of circ-TNPO3. Conclusions Circ-TNPO3 can suppress ccRCC progression and metastasis via directly binding to IGF2BP2 protein and destabilizing SERPINH1 mRNA. Circ-TNPO3 may act as a potential target for ccRCC treatment."

基金机构："National Natural Science Foundation of China [81872392, 82073254]; Scientific Research Foundation for Introduced High-level Personnel in Chongqing Medical University [41021300160256]; Chongqing Talents - Exceptional Young Talents Project [CQYC202005044, cstc2021ycjh-bgzxm0094]; Science and technology research project of Chongqing Municipal Education Commission [KJZD-K202100405]; Future Medical Youth Innovation Team Project of Chongqing Medical University [W0042]; Chongqing Graduate Scientific Research Innovation Project [CYS20211]; Top Graduate Talent Cultivation Program of Chongqing Medical University [BJRC202105]"

基金资助正文："National Natural Science Foundation of China, Grant/Award Numbers: 81872392, 82073254; Scientific Research Foundation for Introduced High-level Personnel in Chongqing Medical University, Grant/Award Number: 41021300160256; Chongqing Talents - Exceptional Young Talents Project, Grant/Award Numbers: CQYC202005044, cstc2021ycjh-bgzxm0094; Science and technology research project of Chongqing Municipal Education Commission, Grant/Award Number: KJZD-K202100405; Future Medical Youth Innovation Team Project of Chongqing Medical University, Grant/Award Number: W0042; Chongqing Graduate Scientific Research Innovation Project, Grant/Award Number: CYS20211; Top Graduate Talent Cultivation Program of Chongqing Medical University, Grant/Award Number: BJRC202105"