CircSTK3 drives the metastasis of colorectal cancer by regulating epithelial-mesenchymal transition
Boyang Fan,
Chaojing Zheng,
Ning Wang,
Zewen Chang,
Yunxiao Liu,
Chunlin Wang,
Jun Xiang,
Yangbao Tao,
Guiyu Wang,
Qian Zhang
Affiliations
Boyang Fan
Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; Corresponding author
Chaojing Zheng
Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
Ning Wang
Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China
Zewen Chang
Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
Yunxiao Liu
Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
Chunlin Wang
Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
Jun Xiang
Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
Yangbao Tao
Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
Guiyu Wang
Department of Colorectal Cancer Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; Corresponding author
Qian Zhang
Department of Colorectal Surgery, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou 310000, China; Corresponding author
Summary: Circular RNAs (circRNAs) play crucial roles in malignancies. We aimed to delineate the functions and clinical importance of dysregulated circRNAs in colorectal cancer (CRC). We determined the circRNA expression profile from five CRC and paired adjacent normal tissues using circRNA microarray. We found that a novel circRNA, hsa_circ_0004592 (named circSTK3), was significantly upregulated in CRC tissues and correlated with decreased survival. Loss- and gain-of-function assays revealed that circSTK3 promoted the migration and invasion but not proliferation of cells. Whole genome expression microarray identified potential downstream targets and the regulatory networks of circSTK3; Gene Ontology analysis confirmed circSTK3 involvement in the CRC metastasis phenotype. Abnormal circSTK3 expression affected a subset of genes associated with CRC metastasis and triggered epithelial-mesenchymal transition programming, maintaining a tumor-promoting signature. Moreover, circSTK3 was transcriptionally regulated by CTCF. These findings reveal the functional and prognostic roles of circSTK3 and expose circRNAs as key players in metastasis.
