MicroRNA-22 suppresses the growth, migration and invasion of colorectal cancer cells through a Sp1 negative feedback loop

// Shu-Sen Xia 1, * , Guang-Jun Zhang 2, 3, * , Zuo-Liang Liu 2, 3 , Hong-Peng Tian 2, 3 , Yi He 2, 3 , Chang-Yuan Meng 4 , Li-Fa Li 5 , Zi-Wei Wang 1 , Tong Zhou 2, 3 1 The Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China 2 The Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China 3 Institute of Hepatobiliary, Pancreatic and Intestinal Disease, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China 4 The Department of Pathology, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China 5 The Department of Medical Microbiology and Parasitology, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China * These authors contributed equally to this work Correspondence to: Zi-Wei Wang, email: wangziwei571@sina.com Tong Zhou, email: zhoutong0088@163.com Keywords: colorectal cancer, miR-22, Sp1, PTEN, AKT Received: October 15, 2016      Accepted: March 21, 2017      Published: March 31, 2017 ABSTRACT MicroRNAs have recently emerged as regulators of many biological processes including cell proliferation, development and differentiation. This study identified that miR-22 was statistically decreased in colorectal cancer clinical specimens and highly metastatic cell lines. Moreover, low miR-22 expression was associated with tumor metastasis, advanced clinical stage and relapse. Consistent with clinical observations, miR-22 significantly suppressed the ability of colorectal cancer cells to growth and metastasize in vitro and in vivo . Sp1 was validated as a target of miR-22, and ectopic expression of Sp1 compromised the inhibitory effects of miR-22. In addition, Sp1 repressed miR-22 transcription by binding to the miR-22 promoter, hence forming a negative feedback loop. Further study has shown that miR-22 suppresses the activity of PTEN/AKT pathway by Sp1. Our present results implicate the newly indentified miR-22/Sp1/PTEN/AKT axis might represent a potential therapeutic target for colorectal cancer.