MiR-181b Influences Colorectal Cancer Progre Ssion By Targeting Tumor Suppressor PDCD4

Colorectal cancer(CRC)is one of the most prevalent malignant tumors,with high morbidity and mortality worldwide.New cases has been increased to 1 million every year,the speed of incidence is increasing to 4.2%.Colorectal cancer has no obvious symptoms at early stage,Metastasis is the main cause leading to death of paitents with CRC.The occurrence and development of colotectal cancer is an extremely complex biological phenomena.It required polygenic participation and multiple stages.Therefore,to work out the mechanism of development and progression of CRC and to find out the preventive and therapeutic methods is the main task in the field of colorectal cancer.microRNA is an abundant class of small noncoding RNAs.19-23 nucleotides(nt)in length,which is capable of degrading mRNA or suppressing translation of the targeted genes with high sequence complementarity.microRNAs are involved in suppression of oncogenes or tumor suppressor genes via complementary binding to their targeted gene transcripts,resulting in gene silencing and thus changes of cellular tumorigenecity in various cancers.There are mounting evidences suggesting that miRNAs have been shown to affect the pathogenesis classification,diagnosis,and prognosis and progression of cancer.Research on the deregulated miRNAs in cancers and finding out their target genes are of vital importance to the understanding and therapy of cancer.In this study,we focused on CRC,and studied how a important miRNAs(oncomiR miR-181b)influenced the progression of CRC by suppressing their targets(tumor suppressor PDCD4).we found that PDCD4 protein levels in tumor tissues were significantly downregulated in three cancer types(CRC,lung cancer and gastric cancer)compared with the adjacent normal tissues.However,the mRNA level of PDCD4 changed little.The inconsistency between PDCD4 protein and mRNA levels prompted us to search for the underlining post-transcriptional regulation mechanism that controlled the downregulation of PDCD4 protein.We focused on miRNAs,which represented a very important post-transcriptional regulation way.We used 3 computational algorithms to predict the possible miRNAs that could target PDCD4 and found that miR-1 81b was an promising candidates.We then checked the level of miR-181b in the 3 cancer tissues mentioned above,and found that miR-181b was significantly upregulated in tumor tissues compared to normal adjacent tissues.What’s more,the fold change of miR-181b was highly reversely correlated with that of PDCD4 protein.We then demonstrated in cells that miR-181b could inhibit PDCD4 protein expression by directly binding to its 3’-UTR.We found that miR-181b could promote CRC cells proliferation and migration in vitro and CRC xenografted tumor growth in vivo by targeting PDCD4.Our results revealed the vital effect of mir-181b on colorectal cancer progression.We wish this result could be beneficial to further elucidating the molecular mechanisms of colorectal cancer and to developing new approaches for molecular therapeutics for this malignant disease.