Circular RNA circ_0089153 acts as a competing endogenous RNA to regulate colorectal cancer development by the miR-198/SUMO-specific peptidase 1 (SENP1) axis

• Published in: Bioengineered Vol. 12; no. 1; pp. 5664 - 5678
• Main Authors: Fang, Guan, Chen, Tingting, Mao, Ruibo, Huang, Xiaming, Ji, Ling
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.01.2021
• Subjects: Animals; Cell Line, Tumor; circ_0089153; Colorectal cancer (CRC); Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Cysteine Endopeptidases - genetics; Cysteine Endopeptidases - metabolism; Female; Humans; Male; Mice; Mice, Inbred BALB C; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miR-198; Research Paper; RNA, Circular - genetics; RNA, Circular - metabolism; SENP1; circ_0089153; miR-198; Colorectal cancer (CRC); SENP1
• ISSN: 2165-5979; 2165-5987
• DOI: 10.1080/21655979.2021.1967076

Increasing evidence has indicated the implications of circular RNAs (circRNAs) in the development of colorectal cancer (CRC). In this study, we investigated the functional role and mechanism of circ_0089153 in CRC pathogenesis. The expression levels of circ_0089153, microRNA (miR)-198, and SUMO-specific peptidase 1 (SENP1) were gauged by quantitative real-time PCR (qRT-PCR) or western blot. Cell proliferation, sphere formation, tube formation, and apoptosis abilities were detected by 5-Ethynyl-2ʹ-Deoxyuridine (EdU), sphere formation, tube formation, and flow cytometry assays, respectively. The direct relationship between miR-198 and circ_0089153 or SENP1 was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The mouse xenograft assays were performed to evaluate the role of circ_0089153 in vivo. Our data showed that circ_0089153 was overexpressed in CRC tissues and cells. Depletion of circ_0089153 repressed cell proliferation, sphere formation ability, and enhanced cell apoptosis, as well as inhibited tube formation in vitro. Moreover, circ_0089153 depletion diminished tumor growth in vivo. Mechanistically, circ_0089153 targeted miR-198, and the effects of circ_0089153 were mediated by miR-198. SENP1 was identified as a direct and functional target of miR-198. Circ_0089153 worked as a competing endogenous RNA (ceRNA) to post-transcriptionally regulate SENP1 expression by miR-198. Our findings identify circ_0089153 as a novel regulator of CRC development through the regulation of the miR-198/SENP1 axis and establish a strong rationale for developing circ_0089153 as a promising therapeutic against CRC.