MicroRNA-22 suppresses the growth, migration and invasion of colorectal cancer cells through a Sp1 negative feedback loop
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Shu-Sen Xia1,*, Guang-Jun Zhang2,3,*, Zuo-Liang Liu2,3, Hong-Peng Tian2,3, Yi He2,3, Chang-Yuan Meng4, Li-Fa Li5, Zi-Wei Wang1, Tong Zhou2,3
1The Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
2The Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China
3Institute of Hepatobiliary, Pancreatic and Intestinal Disease, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China
4The Department of Pathology, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China
5The Department of Medical Microbiology and Parasitology, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China
*These authors contributed equally to this work
Zi-Wei Wang, email: email@example.com
Tong Zhou, email: firstname.lastname@example.org
Keywords: colorectal cancer, miR-22, Sp1, PTEN, AKT
Received: October 15, 2016 Accepted: March 21, 2017 Published: March 31, 2017
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.
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