Interplay of Wnt ß-catenin pathway and miRNAs in HBV pathogenesis leading to HCC.

ABSTRACT

The prevalence of Hepatocellular carcinoma (HCC) has been identified world-wide. Plethora of factors including chronic infection of HBV/HCV has been characterized for the development of HCC. Although the onset and progression of HCC has been linked with awry of various signaling pathways but precise mechanism, still lies under the multitude layers of curiosity. HBV is spreading with insane speed throughout the world and has been found a main culprit in HCC development after regulating the several cellular pathways including Wnt/ß-catenin, Raf/MAPK, Akt and affecting cell multiplication to genomic instability. The role of Wnt/FZD/ß-catenin signaling pathway is centralized in liver functions and its anomalous activation leads to HCC development. ß-catenin mainly plays a pivotal role in canonical pathway of the system. Altered mainly overexpression of ß-catenin along its nuclear localization tunes the aberrations in liver functions and set disease progression. In the development of HCC, modulation of Wnt/FZD/ß-catenin signaling pathway by HBV has been established. As HBV infects the cell it affects the miRNAs, the master regulators of cell. Previous studies showed the connection between HBV and cellular miRNAs. In the present review, we unveiled how HBV is deciphering the cellular miRNAs like miR-26a, miR-15a, miR-16-1, miR-148a, miR-132, miR-122, miR-34a, miR-21, miR-29a, miR-222 and miR-199a/b-3p to modulate the Wnt/FZD/ß-catenin signaling pathway and develop HCC. These HBV mediated miRNAs may prove future therapeutic options to treat HBV-Wnt/FZD/ß-catenin associated HCC.