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Mechanism Investigation of miR-26a’s Regulation of Anoikis in Human Hepatocellular Carcinoma

Author: ZhangXiang
Tutor: YangAnGang; ZhangRui
School: Fourth Military Medical University
Course: Biology
Keywords: HCC miR-26a Integrin Anoikis Chimeric microRNA
CLC: R735.7
Type: Master's thesis
Year: 2012
Downloads: 61
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The role of microRNAs (miRNAs) in human tumorigenesis has beendemonstrated by gene profiling and functional studies. In hepatocellularcarcinoma (HCC), consistently deregulated miRNAs were identified. Mostimportantly, functional and molecular studies uncovered mechanisms that linkedderegulated miRNAs to cancer-associated pathways. In fact, a large number ofstudies have proved that miRNAs themselves could be successfully used for invivo modulation of miRNA actions. The demonstration has shown significantpotentials in molecularly targeted therapy.miR-26a family contains two members, including miR-26a-1andmiR-26a-2. It was reported that, the down-regulation of miR-26was associatedwith not only development of HCC, but also shorter overall survival. Besides,miR-26a was able to inhibit cell proliferation in HCC by targeting CCND2&CCNE2. However, it was report that, about ninety percent of patients with HCCdied from metastasis. So it is very important to identify the relationship between miR-26a and metastasis.In our research, at the beginning, we proved that overexpression ofmiR-26a could promote the anoikis of HCC, in vitro and in vivo. Besides, it wasconfirmed that ITGA5was a target gene of miR-26a, and the ITGA5-lost HCChad similar phenotype with miR-26a-gained HCC. At last but not at least, inrescuing assay, when miR-26a-gained HCC overexpressed ITGA5again, theiranoikis was inhibited. To sum up, we found a new relationship in HCC.MiR-26a promote anoikis in HCC by targeting ITGA5.Based on review and our data, we can make a conclusion that miR-101andmiR-26a are both important tumour suppressor genes. Their coalition may makemore effort in HCC therapy. However, if two kinds of microRNAs are deliveredin the same time, the quantity of each kind of microRNAs is lower, which mustdecrease the effect of each kind of microRNA. So, it is a new problem that howto increase the effect of every single microRNA.In our research, we constructed a kind of chimeric microRNA (CM), whichcontains two seed-sequence-included halves of mature microRNAs. Then, CM’shigh efficiency was confirmed as follows, first, CM’s each seed-sequence-included half had similar function with corresponding nature microRNA.Second, CM’s two seed-sequence-included halves had similar function with twonature microRNAs.

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CLC: > Medicine, health > Oncology > Gastrointestinal Cancer > Liver tumors
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