Abba, M. C. | bioRxiv Science

bioRxiv2021

A non-coding RNA network involved in KSHV tumorigenesis

Regulatory pathways involving non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) and long non-coding RNAs (lncRNA) have gained great relevance due to their role in the control of gene expression modulation. Using RNA sequencing of KSHV Bac36 transfected mouse endothelial cells (mECK36) and tumors, we have analyzed the host and viral transcriptome to uncover the role lncRNA-miRNA-mRNA driven networks in KSHV tumorigenesis. The integration of the differentially expressed ncRNAs, with an exhaustive computational analysis of their experimentally supported targets, led us to dissect complex networks integrated by the cancer-related lncRNAs Malat, Neat1, H19, Meg3 and their associated miRNA-target pairs. These networks would modulate pathways related to KSHV pathogenesis, such as viral carcinogenesis, p53 signaling, RNA surveillance, and Cell cycle control. Finally, the ncRNA-mRNA analysis allowed us to develop signatures that can be used to an appropriate identification of druggable gene or networks defining relevant AIDS-KS therapeutic targets.

cancer biology↗

bioRxiv2020

Requirement for PKC epsilon in KRAS-driven lung tumorigenesis

ABSTRACTNon-small cell lung cancer (NSCLC), the most frequent subtype of lung cancer, remains a highly lethal malignancy and one of the leading causes of cancer deaths worldwide. Mutant KRAS is the prevailing oncogenic driver of lung adenocarcinoma, the most common histological form of NSCLC. In this study, we examined the role of PKCε, an oncogenic kinase highly expressed in NSCLC and other cancers, in KRAS-driven tumorigenesis. Notably, database analysis revealed an association between PKCε expression and poor outcome in lung adenocarcinoma patients specifically having KRAS mutation. By generating a PKCε-deficient, conditionally activatable allele of oncogenic Kras (LSL-KrasG12D;PKCε−/− mice) we were able to demonstrate the requirement of PKCε for Kras-driven lung tumorigenesis in vivo, which is consistent with the impaired transformed growth observed in PKCε-deficient KRAS-dependent NSCLC cells. Moreover, PKCε-knockout mice were found to be less susceptible to lung tumorigenesis induced by benzo[a]pyrene, a carcinogen that induces mutations in Kras. Mechanistic analysis using RNA-Seq revealed little overlapping for PKCε and KRAS in the control of genes/biological pathways relevant in NSCLC, suggesting that a permissive role of PKCε in KRAS-driven lung tumorigenesis may involve non-redundant mechanisms. Our results thus highlight the relevance and potential of targeting PKCε for lung cancer therapeutics.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cancer biology↗