CircMMP1 promotes colorectal cancer growth and metastasis by sponging miR-1238 and upregulating MMP family expression

Weigang Dai; Xiaohui Zhai; Yongming Chen; Yanfang Bai; Hong Deng; Renjie Zhu; Wenhua Fan; Shirong Cai

doi:10.21037/atm-21-3930

CircMMP1 promotes colorectal cancer growth and metastasis by sponging miR-1238 and upregulating MMP family expression

Ann Transl Med. 2021 Aug;9(16):1341. doi: 10.21037/atm-21-3930.

Authors

Weigang Dai^{1

2}, Xiaohui Zhai³, Yongming Chen⁴, Yanfang Bai⁴, Hong Deng⁴, Renjie Zhu⁵, Wenhua Fan⁴, Shirong Cai^{1

2}

Affiliations

¹ Division of Gastrointestinal Surgery Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
² Gastric Cancer Center, Sun Yat-sen University, Guangzhou, China.
³ Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
⁴ Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
⁵ East Hospital Affiliated to Tongji University, Shanghai, China.

Abstract

Background: Circular RNAs (circRNAs) are a type of non-coding RNA which play an important role in the regulation of biological processes of various malignant tumors. However, the potential molecular mechanisms and roles of circRNAs in colorectal cancer (CRC) remain unelucidated.

Methods: In the current study, we analyzed the data of high-throughput microarray sequencing to screen differentially expressed circRNAs in CRC. Cell counting kit-8 (CCK-8), colony-formation, transwell, mouse xenograft models and immunohistochemistry assays were used to explore the function of circRNAs. TargetScan database, quantitative real-time polymerase chain reaction (qRT-PCR), double luciferase and RNA immunoprecipitation (RIP) were used to explore the molecular mechanism.

Results: We identified circMMP1 (hsa_circ_0024109) as a frequently upregulated circRNA in both CRC tissues and cells. Both in vitro and in vivo experiments demonstrated that circMMP1 knockdown significantly inhibited the proliferation and metastasis of CRC. The results demonstrated that circMMP1 promoted the growth and metastasis of CRC by sponging miR-1238 and upregulating the expression of matrix metalloproteinase 1 (MMP1), MMP2, and MMP9 expression.

Conclusions: In conclusion, our study identified the biological role of the circMMP1-miR-1238-MMP1/MMP2/MMP9 axis in the growth and metastasis of CRC, which is crucial for the monitoring and treatment of CRC. Further research on circMMP1 may provide a theoretical basis for diagnostic biomarkers of early CRC screening.

Keywords: MMP; circMMP1; circular RNAs (circRNAs); colorectal cancer (CRC); competing endogenous RNAs (ceRNAs).