PMID- 34740354 OWN - NLM STAT- MEDLINE DCOM- 20220224 LR - 20220224 IS - 1476-4598 (Electronic) IS - 1476-4598 (Linking) VI - 20 IP - 1 DP - 2021 Nov 5 TI - ciRS-7 is a prognostic biomarker and potential gene therapy target for renal cell carcinoma. PG - 142 LID - 10.1186/s12943-021-01443-2 [doi] LID - 142 AB - Circular RNAs are a new class of non-coding RNAs that have been shown to play critical roles in the development and progression of renal cell carcinoma (RCC). However, little is known about the functional mechanisms and therapeutic role of ciRS-7 in RCC. A series of in vitro and in vivo experiments were performed to investigate the functional mechanism and therapeutic role of ciRS-7, such as real-time quantitative PCR, CCK-8, wound healing, transwell, colony formation, Edu, tumor xenograft and lung metastasis in NSG mice. RNA pull-down, dual luciferase reporter, fluorescence in situ hybridization (FISH) and rescue assays were used to determine the relationship between ciRS-7, miR-139-3p and TAGLN. In addition, we constructed PBAE/si-ciRS-7 nanocomplexes with PBAE material to evaluate the therapeutic effect of the nanocomplexes on tumor in vivo. ciRS-7 was highly expressed in RCC tumor tissues and cell lines, and high ciRS-7 expression correlated with tumor size, high Fuhrman grade and poor survival. Depletion of ciRS-7 significantly inhibited RCC cell proliferation, invasion, tumor growth and metastasis in vivo, while overexpression of ciRS-7 had the opposite effect. Mechanistically, ciRS-7 acts as a "ceRNA" for miR-139-3p to prevent TAGLN degradation and promoting RCC progression and metastasis via the PI3K/AKT signaling pathway. In addition, miR-139-3p mimics or inhibitor could reverse the altered malignant tumor behavior caused by ciRS-7 overexpression or silencing. Furthermore, the PBAE/siciRS-7 nanocomplexes could significantly inhibit RCC tumor progression and metastasis in vivo. ciRS-7 acts as a tumor promoter by regulating the miR-139-3p/TAGLN axis and activating the PI3K/AKT signaling pathway to promote RCC progression and metastasis. Drug development of PBAE/si-ciRS-7 nanocomplexes targeting ciRS-7 may represent a promising gene therapeutic strategy for RCC. CI - (c) 2021. The Author(s). FAU - Mao, Weipu AU - Mao W AD - Department of Urology, Affiliated Zhongda Hospital of Southeast University, No. 87 Dingjiaqiao, Hunan Road, Gulou District, Nanjing, 210009, China. AD - Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, 210009, China. AD - Department of Urology, Nanjing Lishui District People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, 211200, China. FAU - Wang, Keyi AU - Wang K AD - Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, No. 301, Yanchang Road, Jing'an District, Shanghai, 200072, China. FAU - Xu, Bin AU - Xu B AD - Department of Urology, Affiliated Zhongda Hospital of Southeast University, No. 87 Dingjiaqiao, Hunan Road, Gulou District, Nanjing, 210009, China. njxb1982@126.com. AD - Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, 210009, China. njxb1982@126.com. AD - Department of Urology, Nanjing Lishui District People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, 211200, China. njxb1982@126.com. FAU - Zhang, Hui AU - Zhang H AD - Department of Anesthesiology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China. FAU - Sun, Si AU - Sun S AD - Department of Urology, Affiliated Zhongda Hospital of Southeast University, No. 87 Dingjiaqiao, Hunan Road, Gulou District, Nanjing, 210009, China. FAU - Hu, Qiang AU - Hu Q AD - Department of Urology, Affiliated Zhongda Hospital of Southeast University, No. 87 Dingjiaqiao, Hunan Road, Gulou District, Nanjing, 210009, China. FAU - Zhang, Lei AU - Zhang L AD - Department of Urology, Affiliated Zhongda Hospital of Southeast University, No. 87 Dingjiaqiao, Hunan Road, Gulou District, Nanjing, 210009, China. FAU - Liu, Chunhui AU - Liu C AD - Department of Urology, Affiliated Zhongda Hospital of Southeast University, No. 87 Dingjiaqiao, Hunan Road, Gulou District, Nanjing, 210009, China. FAU - Chen, Shuqiu AU - Chen S AD - Department of Urology, Affiliated Zhongda Hospital of Southeast University, No. 87 Dingjiaqiao, Hunan Road, Gulou District, Nanjing, 210009, China. FAU - Wu, Jianping AU - Wu J AD - Department of Urology, Affiliated Zhongda Hospital of Southeast University, No. 87 Dingjiaqiao, Hunan Road, Gulou District, Nanjing, 210009, China. FAU - Chen, Ming AU - Chen M AUID- ORCID: 0000-0002-3572-6886 AD - Department of Urology, Affiliated Zhongda Hospital of Southeast University, No. 87 Dingjiaqiao, Hunan Road, Gulou District, Nanjing, 210009, China. mingchenseu@126.com. AD - Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, 210009, China. mingchenseu@126.com. AD - Department of Urology, Nanjing Lishui District People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, 211200, China. mingchenseu@126.com. FAU - Li, Wei AU - Li W AD - Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, No. 301, Yanchang Road, Jing'an District, Shanghai, 200072, China. liweitongji@163.com. FAU - Peng, Bo AU - Peng B AD - Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, No. 301, Yanchang Road, Jing'an District, Shanghai, 200072, China. pengbo6908@163.com. LA - eng GR - 81572517/national natural science foundation of china/ GR - 82070773/national natural science foundation of china/ GR - YBPY2173/scientific research foundation of graduate school of southeast university/ GR - KYCX21_0156/postgraduate research & practice innovation program of jiangsu province/ GR - BE2019751/jiangsu provincial key research and development program/ GR - 2017XKJQW07/innovative team of jiangsu province/ GR - SQ2017YFSF090096/the national key research and development program of china/ PT - Letter PT - Research Support, Non-U.S. Gov't DEP - 20211105 PL - England TA - Mol Cancer JT - Molecular cancer JID - 101147698 RN - 0 (Biomarkers, Tumor) RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - 0 (long non-coding RNA CDR1AS, human) SB - IM EIN - Mol Cancer. 2021 Dec 1;20(1):155. PMID: 34861871 MH - Animals MH - Biomarkers, Tumor/*genetics MH - Carcinoma, Renal Cell/*genetics/metabolism/*mortality/therapy MH - Cell Line, Tumor MH - Cell Movement MH - Cell Proliferation MH - Databases, Genetic MH - Gene Expression Profiling MH - Genetic Therapy MH - Humans MH - Kidney Neoplasms/*genetics/metabolism/*mortality/therapy MH - Mice MH - MicroRNAs/genetics MH - Models, Biological MH - Prognosis MH - RNA Interference MH - RNA, Long Noncoding/*genetics PMC - PMC8570002 OTO - NOTNLM OT - Gene therapeutic OT - Metastasis OT - PBAE/si-ciRS-7 nanocomplexes OT - Renal cell carcinoma OT - ciRS-7 COIS- The authors declare that they have no competing interests. EDAT- 2021/11/07 06:00 MHDA- 2022/02/25 06:00 PMCR- 2021/11/05 CRDT- 2021/11/06 05:21 PHST- 2021/06/28 00:00 [received] PHST- 2021/10/05 00:00 [accepted] PHST- 2021/11/06 05:21 [entrez] PHST- 2021/11/07 06:00 [pubmed] PHST- 2022/02/25 06:00 [medline] PHST- 2021/11/05 00:00 [pmc-release] AID - 10.1186/s12943-021-01443-2 [pii] AID - 1443 [pii] AID - 10.1186/s12943-021-01443-2 [doi] PST - epublish SO - Mol Cancer. 2021 Nov 5;20(1):142. doi: 10.1186/s12943-021-01443-2.