The circular RNA circSPARC enhances the migration and proliferation of colorectal cancer by regulating the JAK/STAT pathway

• Published in: Molecular cancer 2021-06, Vol.20 (1), p.81-81, Article 81
• Main Authors: Wang, Jiaqi, Zhang, Yi, Song, Hu, Yin, Hang, Jiang, Tao, Xu, Yixin, Liu, Lianyu, Wang, Hongyu, Gao, Hong, Wang, Renhao, Song, Jun
• Format: Article
• Language: English
• Subjects: Adult; Aged; Analysis; Animals; Binding sites; Biomarker; Biomarkers; Cell adhesion & migration; Cell cycle; Cell growth; Cell migration; Cell Movement - genetics; Cell Proliferation - genetics; Chromatin; circRNA; circSPARC; Circular RNA; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - pathology; Cytokines; Development and progression; Female; Fluorescence in situ hybridization; Gene expression; Gene Expression Regulation, Neoplastic - genetics; Health aspects; Heterografts; Humans; Immunoprecipitation; JAK/STAT signalling pathway; Janus kinase 2; Janus Kinase 2 - metabolism; Kinases; Lymph nodes; Male; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs; Middle Aged; mRNA; Nuclear transport; Osteonectin - genetics; Osteonectin - metabolism; RNA; RNA, Circular - genetics; RNA, Circular - metabolism; Signal Transduction - physiology; Stat3 protein; STAT3 Transcription Factor - metabolism; Surgery; Therapeutic targets; Western blotting; Wound healing
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/s12943-021-01375-x

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. 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. 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. 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.