Expression analysis of Rho GTPase-related lncRNAs in breast cancer

The Rho GTPases have prominent roles in cell cycle transition and cell migration. Some members of this family have been found to be mutated in cancers. Moreover, alterations in expression levels and/or activity of these proteins have been reported in many types of cancers. Thus, Rho GTPases are involved in the carcinogenesis. Rho GTPases regulate growth, motility, invasiveness and metastatic ability of breast cancer cells. Long non-coding RNAs (lncRNAs) have been revealed to exert significant effect in the regulation of these proteins via direct routes or through sequestering microRNAs that inhibit Rho GTPases. We aimed to assess expression levels of four Rho GTPase-related lncRNAs, namely NORAD, RAD51-AS1, NRAV and DANCR in breast cancer samples versus non-cancerous specimens from the same individuals. Expression levels of NORAD were shown to be elevated in tumoral tissues compared with non-tumoral tissues (Expression ratio (95% CI)= 5.85 (3.16-10.83), Standard error of mean (SEM)= 0.44, P value< 0.0001). NRAV expression was also higher in tumoral tissues compared with control tissues (Expression ratio=2.85 (1.52-5.35), SEM= 0.45, P value= 0.0013). Similar to these lncRNAs, RHOA was demonstrated to be up-regulated in malignant tissues (Expression ratio=6.58 (3.17-13.63), SEM= 0.52, P value< 0.0001). Although expression ratio values showed up-regulation of RAD51-AS1 and DANCR in cancerous tissues (Expression ratio (95% CI)= 2.2 (1.05-4.6) and 1.35 (0.72-2.53), respectively), P values did not reach significance level (P values=0.0706 and 0.3746, respectively). There were significant as-sociations between expression level of NRAV gene in tumor tissues and a number of parameters including age, histological tumor grade and tubule formation. Taken together, the current study shows dysregulation of a number of RHOA-related lncRNAs in breast cancer in association with abnormal up-regulation of this member of Rho GTPase family and suggests conduction of additional functional studies to unravel their mode of partici-pation in the breast carcinogenesis.