Long non-coding RNA (lncRNA) five prime to Xist (FTX) promotes retinoblastoma progression by regulating the microRNA-320a/with-no-lysine kinases 1 (WNK1) axis

Abstract

Long non-coding RNA (lncRNA) five prime to Xist (FTX) exerts important functions in human cancer, while its role in retinoblastoma (RB) remains unclear. This study aimed to investigate the role of FTX in RB. The expression levels of FTX were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was evaluated by cell counting kit-8 (CCK-8), 5‐ethynyl‐2′‐deoxyuridine (EdU) staining and colony formation assays. Cell migration and invasion were detected by Transwell assay. The relationship among FTX, microRNA-320a (miR-320a) and with-no-lysine kinase 1 (WNK1) was also investigated. In the present study, we found that the expression levels of FTX were notably elevated in RB tissues and cancer cell lines. Overexpression of FTX exacerbated the aggressive phenotypes (cell proliferation, migration and invasion) of RB cells. Downregulation of miR-320a obviously attenuated the inhibitory effects of knockdown of FTX in RB malignant phenotypes, and knockdown of WNK1 also reversed the impacts of miR-320a inhibitor on malignant phenotypes. In vivo experiments further confirmed that knockdown of FTX efficiently prevents tumor growth in vivo . Our results revealed that FTX promoted RB progression by targeting the miR-320a/WNK1 axis (graphical abstract), suggesting that FTX might be a novel therapeutic target for RB.

An update regarding the role of WNK kinases in cancer

“…MiR-93, miR-130a, miR-210a, miR-524a, and miR-620 are found to directly target oncogenic WNK1/3 or antitumor WNK2, thus affecting cancer progression [ 101 , 107 , 109 , 117 – 119 ]. However, the inhibitory effect of these miRNAs on WNK expression can be released by the “sponge effect” of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), such as lncRNA FTX, lncRNA H19 and circRNA circ_0001666 [ 109 , 118 , 119 ]. In addition, recent studies have found that lncRNA LINC00858 can directly repress the expression of WNK2 in cancer cells and contribute to cancer progression [ 87 , 106 , 108 ].…”

WNK1–OSR1 Signaling Regulates Angiogenesis-Mediated Metastasis towards Developing a Combinatorial Anti-Cancer Strategy

“…WNK1 is involved in many cancers including liver cancer, breast cancer, glioblastoma, giant cell tumors, retinoblastoma, clear-cell renal-cell carcinoma, and lung adenocarcinoma [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. NKCC1 overexpression enhances the proliferation and invasion of HCC cells through the WNK1–OSR1–NKCC1 pathway [ 18 ].…”