Here we studied the cell to cell communication through exosomal components such as proteins and non-coding RNAs including microRNA, circular RNA, long non-coding RNA etc.. Right now we are interested in making sense on the cross-communication between cancer cells, cancer-associated macrophages, T-lymphocytes and cancer-associated fibroblasts. Proteomics, transcriptomics, Bioinformatics analysis, CRISPR tools, 2D and 3D culture, Confocal and Electron microscopy, FACS and Real time PCR are mainly employed for such study. Our proteomics analysis of exosomes derived from HepG2.2.15 (Stable HBV-producing cells) and HepG2 (Control) cells revealed a bunch of RNA-binding proteins enriched in the exosomes and some of them have important contributions to the M2 polarization of macrophages suggesting their potential to be a therapeutic target. Also, the descendent analysis of total RNA sequencing (NGS) from HCV-HCC human liver tissues revealed some significantly upregulated lncRNAs, some of which can be loaded inside the exosomes and can have immunomodulatory effects in tumor immune-microenvironment in HCC.
In this study, we searched for the mechanism of suppression of tumor suppressor miRNAs in HCC. We selected miRNAs from small RNA transcriptome analysis of HCC liver tissue samples and studied their mechanism of function as genome protectors. Do they function convergently? Is there any master regulator for all suppressed miRNAs? Does long non-coding RNA play any role here to sponge miRNAs? Who could be a probable target for HCC?
Here we selected the circular RNA and telomeric proteins having role in the development of stemness and chemoresistance i.e., sorafenib resistance in HCC. Here, we are trying to explore that circRNA/telomeric gene mediated downstream axis to reveal the regulatory signaling and its effect on the generation of sorafenib resistance in case of advanced HCC patients.
Here we searched for oncogene MYC-deregulated miRNAs using bioinformatics tools and observed among the upregulated miRNAs in HBV-HCC, miR-126-5p has 16 MYC binding sites. Subsequently, we found this miRNA could target beta-catenin destruction complex and releases beta-catenin which induces expression of MYC and it induces stemness markers, EMT markers, and cell becomes chemo-resistant. This data suggest miR-126-5p could be a potential therapeutic target for HCC.
Here we mapped the transcript variants accumulated in HCC using NGS data and observed multiple novel splice variants. Among these SVs, N-terminal deleted SCARB1-SV is characterized here, and observed this novel protein resides within the cytoplasm instead of the plasma membrane and triggers chemo-resistance to HCC cells.