LncRNA Linc-PINT inhibits miR-523-3p to hamper retinoblastoma progression by upregulating Dickkopf-1 (DKK1).

Emerging evidences indicated that long non-coding RNAs (LncRNAs) regulated the pathogenesis of retinoblastoma (RB). However, up until now, the role of LncRNA Linc-PINT in the regulation of RB progression is still largely unknown. The present study identified LncRNA Linc-PINT as a tumor suppressor to hinder RB development by regulating miR-523-3p/Dickkopf-1 (DKK1) axis. Mechanistically, Linc-PINT was low-expressed, while miR-523-3p was high-expressed in RB cells, compared to the normal retinal epithelial cells (ARPE-19). Further gain- and loss-function experiments verified that both upregulation of Linc-PINT and miR-523-3p downregulation slowed down cell growth, invasion and migration, and promoted cell apoptosis in RB cells, but Linc-PINT ablation and miR-523-3p overexpression promoted malignant phenotypes in RB cells. In addition, the dual-luciferase reporter gene system and RNA pull-down assay validated that Linc-PINT positively regulated DKK1 expressions by sponging miR-523-3p, and Linc-PINT inhibited RB progression by regulating miR-523-3p/DKK1 axis. Functionally, we found that both miR-523-3p overexpression and DKK1 silence abrogated the anti-cancer effects of overexpressed Linc-PINT on RB cells. Finally, Linc-PINT inhibited tumorigenicity of RB cells in xenograft mice models. In general, analysis of the data suggested that Linc-PINT inhibited miR-523-3p to upregulate DKK1, resulting in the inhibition of RB, and we demonstrated that Linc-PINT and miR-523-3p could be utilized as potential diagnostic and therapeutic biomarkers for RB in clinic.

LncRNA ZNF667-AS1 Targets miR-523-3p/KIF5C Axis to Hinder Colon Cancer Progression.

LncRNA ZNF667-AS1 plays an important role in the carcinogenesis and progression of various cancers. However, their role in colon cancer (CC) remains unclear. The expression of ZNF667-AS1, KIF5C, and miR-523-3p in CC cells and tissues was analyzed using RT-qPCR and western blotting. CCK-8 scratch-wound assay, western blotting, and flow cytometry were conducted to investigate the malignant activity of CC in vitro. Luciferase reporter, RNA pull-down, and Ago2 immunoprecipitation (RIP) experiments were conducted to ascertain the association of miR-523-3p with ZNF667-AS1 and KIF5C 3'UTR. Xenograft tumor experiments were also performed. CC cells and tissues showed low expression of NF667-AS1 and KIF5C and elevated expression of miR-523-3p. ZNF667-AS1 overexpression attenuates proliferation and migration of CC cells, restores inactivated apoptosis in vitro, and inhibits tumor growth in vivo. MiR-523-3p targets both ZNF667-AS1 and the KIF5C 3'UTR. ZNF667-AS1 overexpression in SW480 and SW620 cells attenuated the oncogenic effect of miR-523-3p in CC. However, this attenuating effect was counteracted by KIF5C overexpression. ZNF667-AS1 sequestered miR-523-3, reducing miR-523-3p-mediated inhibition of KIF5C expression, thereby repressing colon carcinogenesis in vitro. Our findings shed light on a novel anticancer strategy that could potentially combat CC.

LncRNA ZNF667-AS1 alleviates rheumatoid arthritis by sponging miR-523-3p and inactivating the JAK/STAT signalling pathway.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease, which compromises the synovial membrane resulting in chronic inflammation. Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) are implicated in the pathogenesis of RA. This study investigated the role of lncRNA ZNF667-AS1 in RA progression. METHODS: Synovial tissues and fibroblast-like synoviocytes (FLSs) were obtained from patients with RA. Gene expression was measured using RT-qPCR. Chondrocytes were treated with lipopolysaccharide (LPS) to establish in vitro models of OA. Cell counting kit-8 (CCK-8), western blot, and enzyme-linked immunosorbent assay (ELISA) were used to examine the proliferation and inflammatory cytokine production in chondrocytes. Animal models of OA were established in SD rats. Peripheral blood mononuclear cells (PBMCs) were isolated from the OA rats. Flow cytometry was used to measure the changes of the inflammatory T-helper cell 17 (Th17) cells. The relationship between ZNF667-AS1 and miR-523-3p was verified by luciferase reporter assay. RESULTS: ZNF667-AS1 was downregulated in RA-FLSs and LPS-stimulated chondrocytes. ZNF667-AS1 overexpression significantly promoted cell proliferation and inhibited the production of IL-6, IL-17 and TNF-α in LPS-stimulated chondrocytes. Additionally, ZNF667-AS1 overexpression reduced the generation of CD4 + IL-17+ cells. In mechanism, ZNF667-AS1 acted a sponge for miR-523-3p. MiR-523-3p overexpression reversed the ZNF667-AS1-mediated regulation of cell proliferation and inflammation. Furthermore, miR-523-3p overexpression abolished the inhibitory effects of ZNF667-AS1 on the JAK/STAT signalling activation. CONCLUSION: ZNF667-AS1 exerts protective effects during RA development by sponging miR-523-3p and inactivating the JAK/STAT signalling.