LncRNA HOTAIR/miR‐613/c‐met axis modulated epithelial‐mesenchymal transition of retinoblastoma cells

Abstract

Since lncRNAs could modulate neoplastic development by modulating downstream miRNAs and genes, this study was carried out to figure out the synthetic contribution of HOTAIR, miR‐613 and c‐met to viability, apoptosis and proliferation of retinoblastoma cells. Totally 276 retinoblastoma tissues and tumour‐adjacent tissues were collected, and human retinoblastoma cell lines (ie, Y79, HXO‐Rb44, SO‐Rb50 and WERI‐RB1) were also gathered. Moreover, transfections of pcDNA3.1‐HOTAIR, si‐HOTAIR, miR‐613 mimic, miR‐613 inhibitor, pcDNA3.1/c‐met were performed to evaluate the influence of HOTAIR, miR‐613 and c‐met on viability, apoptosis and epithelial‐mesenchymal transition (EMT) of retinoblastoma cells. Dual‐luciferase reporter gene assay was also arranged to confirm the targeted relationship between HOTAIR and miR‐613, as well as between miR‐613 and c‐met. Consequently, up‐regulated HOTAIR and down‐regulated miR‐613 expressions displayed associations with poor survival status of retinoblastoma patients (P < 0.05). Besides, inhibited HOTAIR and promoted miR‐613 elevated E‐cadherin expression, yet decreased Snail and Vimentin expressions (P < 0.05). Simultaneously, cell proliferation and cell viability were also less‐motivated (P < 0.05). Nonetheless, c‐met prohibited the functioning of miR‐613, resulting in promoted cell proliferation and viability, along with inhibited cell apoptosis (P < 0.05). Finally, HOTAIR was verified to directly target miR‐613, and c‐met was the direct target gene of miR‐613 (P < 0.05). In conclusion, the role of lncRNA HOTAIR/miR‐613/c‐met signalling axis in modulating retinoblastoma cells’ viability, apoptosis and expressions of EMT‐specific proteins might provide evidences for developing appropriate diagnostic and treatment strategies for retinoblastoma.

lncRNA HOTAIR overexpression induced downregulation of c-Met signaling promotes hybrid epithelial/mesenchymal phenotype in hepatocellular carcinoma cells

“…This analysis supports our data showing HOTAIR downregulation is a requirement for c-Met activation and c-Met triggered complete mesenchymal phenotype in HCC cell lines. Contrary to the reports of melanoma, retinoblastoma and colon cancer studies [47][48][49] and expectations on the parallel expression tendencies of c-Met and HOTAIR in HCC cell lines; comparative analysis of HCC cell lines and cancer datasets shows the opposite, clearly. Indicated studies suggested HOTAIR as a competing long non-coding RNA decoying microRNAs targeting c-Met in different cancer contexts, and those microRNAs are reported to have different molecular targets in HCC rather than c-Met [50,51].…”

Non-Coding RNAs in Pediatric Solid Tumors

“…In retinoblastoma, HOTAIR, THOR, and MEG3 appear to have a similar influence as seen in osteosarcoma, where they also acted as oncogenes (HOTAIR and THOR) or tumor suppressors (MEG3) (Gao et al, 2017; Shang, 2018; Yang G. et al, 2018). In the study examining HOTAIR in retinoblastoma, HOTAIR was shown to be engaged in a reciprocal regulatory loop with miR-613 and promoted cell proliferation and activation of the EMT, potentially through upregulation of N-cadherin, vimentin, and α‐SMA (Yang G. et al, 2018). Several lncRNAs have also been found acting as oncogenic ceRNAs including XIST, DANCR, and HOXA11-AS (Hu et al, 2018; Wang J. X. et al, 2018; Han et al, 2019).…”

Knockdown of Long Non-coding RNA UCA1 Represses Gallbladder Cancer Advancement by Regulating SPOCK1 Expression via Sponging miR-613

“…It was reported that miR-613 mimic could repress Daam1 expression in triple-negative breast cancer, which impeded cell invasion and migration [15]. Yang et al reported that lncRNA HOTAIR enhanced c-met expression via sponging miR-613, which facilitated cell the epithelial-mesenchymal transition in retinoblastoma [29]. However, Yang et al pointed out that miR-613 accelerated colon cancer progression via repressing ATOH1 expression [30].…”