Abstract
MicroRNAs (miRNAs) are a class of small, noncoding RNAs that act as key regulators in various physiological and pathological processes. However, the regulatory mechanisms for miRNAs in colorectal cancer remain largely unknown. Here, we found that miR-103 is up-regulated in colorectal cancer and its overexpression is closely associated with tumor proliferation and migration. In addition, repressing the expression of miR-103 apparently inhibits colorectal cancer cell proliferation and migration in vitro and HCT-116 xenograft tumor growth in vivo. Subsequent software analysis and dual-luciferase reporter assay identified two tumor suppressor genes DICER and PTEN as direct targets of miR-103, and up-regulation of DICER and PTEN obtained similar results to that occurred in the silencing of miR-103. In addition, restoration of DICER and PTEN can inhibit miR-103-induced colorectal cancer cell proliferation and migration. Our data collectively demonstrate that miR-103 is an oncogene miRNA that promotes colorectal cancer proliferation and migration through down-regulation of the tumor suppressor genes DICER and PTEN. Thus, miR-103 may represent a new potential diagnostic and therapeutic target for colorectal cancer treatment.
Highlights
Colorectal cancer is the third most commonly diagnosed cancer worldwide, especially in developed countries [1,2], with symptoms like rectal bleeding and anemia sometimes associated with weight loss and changes in bowel habits [3,4]
In order to investigate the roles of miRNAs that played in colorectal cancer, we did a microarray and we found that miR-103 is one of the most significantly up-regulated miRNA in colorectal cancers and the proliferation of colorectal cancer cells is apparently repressed when miR-103 was silenced
The expression of miR-103 was significantly higher in cancer cells than that in normal control. These data uncovered that the expression of miR-103 was universally up-regulated in colorectal cancer cells and patients, indicating that increased miR-103 expression might contribute to tumor malignant phenotype and tumor development
Summary
Colorectal cancer is the third most commonly diagnosed cancer worldwide, especially in developed countries [1,2], with symptoms like rectal bleeding and anemia sometimes associated with weight loss and changes in bowel habits [3,4]. MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally modulate gene expression by repressing translation or accelerating mRNA degradation [8,9] They are highly conserved among species and play important roles in various physiological and pathological processes including developmental abnormalities, autoimmune diseases and cancers [10,11,12]. When used in combination with miR-103, both DICER and PTEN apparently abrogated the effect of miR-103 on colorectal cancer cell proliferation and migration. To verify all these in vitro data, xenograft models were generated by HCT-116 cells with up-regulated or down-regulated miR-103 levels (transfected by lenti-miR-103 or agomir-miR-103, respectively), results showed that up-regulation of miR-103 significantly promoted, whereas down-regulation of miR-103 inhibited the growth of xenografts in vivo. Our study demonstrated that miR-103 may represent a new potential therapeutic target for colorectal carcinoma treatment by targeting DICER and PTEN
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