الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Hepatocellular carcinoma (HCC), the most common primary malignant tumor evolving in the liver, accounts for >90% of all primary liver tumor. Besides, HCC is the third leading cause of cancer-related death. Most therapies available are not effective hence stressing the need for effective alternative therapeutics. MicroRNAs (miRNAs) are class of evolutionarily conserved small non-coding RNAs. They potentially control the expression multiple oncogenes at the post transcriptional level. In the current study, an integrative in silico analysis for three potent tumor suppressor miRs in HCC (let-7a, miR-34a and miR-199) was performed. The regulation of these miRs on specific target genes and pathways in HCC was revealed. In addition, the findings of the in silico analysis were validated by in vitro experiments. These experiments based mainly on testing the effect of re-expression of the tumor suppressor miRs through specific vector expressing the mature miRs in the tested HCC cell line (HepG2). Overall, the present study could suggest the following:
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Summary
1) The combinatorial functional analysis of let-7a, miR-34a and miR-199 by miRror Suite and DAVID revealed that these three miRs cooperatively regulate multiple oncogenic targets and pathways of HCC and especially immune system pathways.
2) The individual functional analysis of let-7a, miR-34a and miR-199 by miRGator, GeneTrail and miRWalk revealed that each miRNA regulate specific set of multiple oncogenic targets and pathways of HCC and especially immune system pathways.
3) High transfection efficiency of pEGP-vectors expressing mature miRs in HepG2, led to significant high expression of mature miRs in the treated cells reaching to ∼20 fold over-expression as measured by qPCR.
4) Significant low expression of three common novel oncogenes (FNDC3B, IGF2 and SOX4) of the tumor suppressor miRs reaching to ∼69 fold downregulation as measured by qPCR.
5) Significant suppression in the proliferation rate of HepG2 cells after treatment with miRs as it evaluated by MTT assay. The proliferation rate of cells was decreased by ∼39 %.
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Summary
Collectively, let-7a, miR-34a and miR-199 are three important tumor suppressor miRs in HCC and they can further efficiently tested by in vivo models and clinical trials to be used as alternative anti-HCC therapeutics