KRAS mutation is responsible for 40–50% of colorectal cancers (CRCs). RNA-seq data and bioinformatics methods were used to analyze the transcriptional profiles of KRAS mutant (mtKRAS) in comparison with the wild-type (wtKRAS) cell lines, followed by in-silico and quantitative real-time PCR (qPCR) validations. Gene set enrichment analysis showed overrepresentation of KRAS signaling as an oncogenic signature in mtKRAS. Gene ontology and pathway analyses on 600 differentially-expressed genes (DEGs) indicated their major involvement in the cancer-associated signal transduction pathways. Significant hub genes were identified through analyzing PPI network, with the highest node degree for PTPRC. The evaluation of the interaction between co-expressed DEGs and lncRNAs revealed 12 differentially-expressed lncRNAs which potentially regulate the genes majorly enriched in Rap1 and RAS signaling pathways. The results of the qPCR showed the overexpression of PPARG and PTGS2, and downregulation of PTPRC in mtKRAS cells compared to the wtKRAS one, which confirming the outputs of RNA-seq analysis. Further, significant upregualtion of miR-23b was observed in wtKRAS cells. The comparison between the expression level of hub genes and TFs with expression data of CRC tissue samples deposited in TCGA databank confirmed them as distinct biomarkers for the discrimination of normal and tumor patient samples. Survival analysis revealed the significant prognostic value for some of the hub genes, TFs, and lncRNAs. The results of the present study can extend the vision on the molecular mechanisms involved in KRAS-driven CRC pathogenesis.

RHO GTPases are critical signal transducers that regulate cell adhesion, polarity, and migration through multiple signaling pathways. While all these cellular processes are crucial for the maintenance of normal cell homeostasis, disturbances in RHO GTPase-associated signaling pathways contribute to different human diseases, including many malignancies. Several members of the RHO GTPase family are frequently upregulated in human tumors. Abnormal gene regulation confirms the pivotal role of lncRNAs as critical gene regulators, and thus, they could potentially act as oncogenes or tumor suppressors. lncRNAs most likely act as sponges for miRNAs, which are known to be dysregulated in various cancers. In this regard, the significant role of miRNAs targeting RHO GTPases supports the view that the aberrant expression of lncRNAs may reciprocally change the intensity of RHO GTPase-associated signaling pathways. In this review article, we summarize recent advances in lncRNA research, with a specific focus on their sponge effects on RHO GTPase-targeting miRNAs to crucially mediate gene expression in different cancer cell types and tissues. We will focus in particular on five members of the RHO GTPase family, including RHOA, RHOB, RHOC, RAC1, and CDC42, to illustrate the role of lncRNAs in cancer progression. A deeper understanding of the widespread dysregulation of lncRNAs is of fundamental importance for confirmation of their contribution to RHO GTPase-dependent carcinogenesis.

Epithelial ovarian cancer (EOC), as a challenging disease among women with poor prognosis and unclear molecular pathogenesis, each year is responsible for 140000 deaths globally. Recent progress in the field revealed the importance of proteins as key players of different biological events. Considering the complicated protein interactions, taking a deeper look at protein-protein interactions (PPIs) could be considered as a superior strategy to unravel complex mechanisms encountered with regulatory cell signaling pathways of ovarian cancer. Hence, PPI network analysis was performed on differentially expressed genes (DEGs) of ovarian cancer to discover hub genes which have the potential to be introduced as biomarkers with clinical utility. A PPI network with 600 DEGs was constructed. Network topology analysis determined UBC, FN1, SPP1, ACTB, GAPDH, JUN, and RPL13A, with the highest Degree (K) and betweenness centrality (BC), as shortcuts of the network. KEGG pathway analysis showed that these genes are commonly enriched in ribosome and ECM-receptor interaction pathways. These pivotal hub genes, mainly UBC, FN1, RPL13A, SPP1, and JUN have been reported previously as potential prognostic biomarkers of different types of cancer. However, further experimental molecular studies and computational processes are required to confirm the function and association of the identified hub genes with epithelial ovarian cancer prognosis.