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.
Highlights
In China, the incidence of colorectal cancer(CRC) is continually increasing despite advances in treatment and subsequent improvement in prognosis [1]
Our previous study showed that the expression of miR-22 was significantly lower in CRC tissues, and low expression of miR-22 was correlated with liver metastasis [20]
We investigated the miR-22 expression level in an expanded CRC cohort consisting of 118 pairs of primary CRC and their matched normal tissues. 76% (83 of 118) of the CRC patients had reduced miR-22 expression by at least 4-fold as compared with their matched normal tissues (Figure 1A), and miR-22 correlated with tumor progression as it was decreased in the sequence from stage I to stage IV CRC (Figure 1B)
Summary
In China, the incidence of colorectal cancer(CRC) is continually increasing despite advances in treatment and subsequent improvement in prognosis [1]. It has been revealed that the altered expression or activity of specific genes, including microRNAs (miRNAs), is involved in the pathogenesis of CRC [2, 3]. MiRNAs regulate the expression of a wide variety of target genes, and are involved in a wide range of biological processes [6, 7]. Among the deregulated miRNAs, miR-22 is widely studied in various cancers, including CRC [10,11,12,13,14,15,16,17,18,19]. Our previous studies have suggested that miR-22 is significantly down-regulated in CRC tissues and low expression of miR-22 correlated with distant metastases and poor prognosis of CRC [20]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
