PMID- 34074294 OWN - NLM STAT- MEDLINE DCOM- 20220111 LR - 20220111 IS - 1476-4598 (Electronic) IS - 1476-4598 (Linking) VI - 20 IP - 1 DP - 2021 Jun 1 TI - The circular RNA circSPARC enhances the migration and proliferation of colorectal cancer by regulating the JAK/STAT pathway. PG - 81 LID - 10.1186/s12943-021-01375-x [doi] LID - 81 AB - BACKGROUND: Noncoding RNAs such as circular RNAs (circRNAs) are abundant in the human body and influence the occurrence and development of various diseases. However, the biological functions of circRNAs in colorectal cancer (CRC) are largely unknown. METHODS: RT-qPCR was used to detect the expression of circRNAs and mRNA in CRC cells and tissues. Fluorescence in situ hybridization (FISH) was used to analyze the location of circSPARC. Function-based experiments were performed using circSPARC knockdown and overexpression cell lines in vitro and in vivo, including CCK8, colony formation, transwell and metastasis models. Mechanistically, luciferase reporter assay, western blots, RNA immunoprecipitation (RIP), Chromatin isolation by RNA purification (ChIRP) and immunohistochemical stainings were performed. RESULTS: CircSPARC was upregulated in both the tissues and plasma of CRC patients. High expression of circSPARC was associated with advanced TNM stage, lymph node metastases, and poor survival. Silencing circSPARC inhibited CRC cell migration and proliferation in vitro and vivo. Mechanistically, circSPARC sponged miR-485-3p to upregulate JAK2 expression and ultimately contribute to the accumulation of phosphorylated (p)-STAT3. Besides, circSPARC recruited FUS, which facilitated the nuclear translocation of p-STAT3. CONCLUSIONS: These findings suggest that circSPARC might serve as a potential diagnostic and prognostic biomarker and a therapeutic target for CRC treatment by regulating JAK2/STAT3 pathway. FAU - Wang, Jiaqi AU - Wang J AD - Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, Jiangsu Province, China. AD - Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu Province, China. FAU - Zhang, Yi AU - Zhang Y AD - Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, Jiangsu Province, China. FAU - Song, Hu AU - Song H AD - Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, Jiangsu Province, China. FAU - Yin, Hang AU - Yin H AD - Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu Province, China. FAU - Jiang, Tao AU - Jiang T AD - Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, Jiangsu Province, China. FAU - Xu, Yixin AU - Xu Y AD - Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, Jiangsu Province, China. FAU - Liu, Lianyu AU - Liu L AD - Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, Jiangsu Province, China. AD - Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu Province, China. FAU - Wang, Hongyu AU - Wang H AD - Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, Jiangsu Province, China. AD - Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu Province, China. FAU - Gao, Hong AU - Gao H AD - Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu Province, China. FAU - Wang, Renhao AU - Wang R AUID- ORCID: 0000-0002-4465-9953 AD - Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, Jiangsu Province, China. wangrenhao@xzhmu.edu.cn. AD - Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu Province, China. wangrenhao@xzhmu.edu.cn. FAU - Song, Jun AU - Song J AUID- ORCID: 0000-0002-6350-2695 AD - Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, Jiangsu Province, China. songjunwk@126.com. AD - Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221002, Jiangsu Province, China. songjunwk@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210601 PL - England TA - Mol Cancer JT - Molecular cancer JID - 101147698 RN - 0 (Osteonectin) RN - 0 (RNA, Circular) RN - 0 (SPARC protein, human) RN - 0 (STAT3 Transcription Factor) RN - 0 (STAT3 protein, human) RN - EC 2.7.10.2 (JAK2 protein, human) RN - EC 2.7.10.2 (Janus Kinase 2) SB - IM MH - Adult MH - Aged MH - Animals MH - Cell Movement/genetics MH - Cell Proliferation/genetics MH - Colorectal Neoplasms/*pathology MH - Female MH - Gene Expression Regulation, Neoplastic/*genetics MH - Heterografts MH - Humans MH - Janus Kinase 2/*metabolism MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Middle Aged MH - Osteonectin/genetics/*metabolism MH - RNA, Circular/genetics/*metabolism MH - STAT3 Transcription Factor/*metabolism MH - Signal Transduction/physiology PMC - PMC8167978 OTO - NOTNLM OT - Biomarker OT - Colorectal cancer OT - JAK/STAT signalling pathway OT - circRNA OT - circSPARC COIS- The authors declare that they have no conflicts of interest. EDAT- 2021/06/03 06:00 MHDA- 2022/01/12 06:00 PMCR- 2021/06/01 CRDT- 2021/06/02 05:37 PHST- 2020/12/17 00:00 [received] PHST- 2021/05/19 00:00 [accepted] PHST- 2021/06/02 05:37 [entrez] PHST- 2021/06/03 06:00 [pubmed] PHST- 2022/01/12 06:00 [medline] PHST- 2021/06/01 00:00 [pmc-release] AID - 10.1186/s12943-021-01375-x [pii] AID - 1375 [pii] AID - 10.1186/s12943-021-01375-x [doi] PST - epublish SO - Mol Cancer. 2021 Jun 1;20(1):81. doi: 10.1186/s12943-021-01375-x.