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长链非编码 RNA FEZF1-AS1 通过调控 miR-363-3p/PAX6 轴促进视网膜母细胞瘤的生长并减少细胞凋亡。

Long Non-coding RNA FEZF1-AS1 Promotes Growth and Reduces Apoptosis Through Regulation of miR-363-3p/PAX6 Axis in Retinoblastoma.

机构信息

Department of Ophthalmology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, No. 1, Huanghe Road, Huaiyin District, Huaian, 223300, Jiangsu, China.

出版信息

Biochem Genet. 2021 Jun;59(3):637-651. doi: 10.1007/s10528-020-10026-7. Epub 2021 Jan 11.

Abstract

Retinoblastoma is the most common malignancy in children's eyes with high incidence. Long non-coding RNAs (lncRNAs) play important roles in the progression of retinoblastoma. LncRNA FEZF1 antisense RNA 1 (FEZF1-AS1) has been found to stimulate retinoblastoma. However, the mechanism of FEZF1-AS1 underlying progression of retinoblastoma is still unclear. In current study, FEZF1-AS1 was up-regulated in retinoblastoma tissues and cells. FEZF1-AS1 overexpression enhanced retinoblastoma cell viability, promoted cell cycle, and inhibited apoptosis. Conversely, FEZF1-AS1 knockdown reduced cell viability, cycle, and elevated apoptosis. The interaction between FEZF1-AS1 and microRNA-363-3p (miR-363-3p) was confirmed. FEZF1-AS1 down-regulated miR-363-3p and up-regulated PAX6. PAX6 was a target gene of miR-363-3p. EZF1-AS1 promoted retinoblastoma cell viability and suppressed apoptosis via PAX6. Further, we demonstrated that FEZF1-AS1 contribute to tumor formation in vivo. In conclusion, FEZF1-AS1 elevated growth and inhibited apoptosis by regulating miR-363-3p/PAX6 in retinoblastoma, which provide a new target for retinoblastoma treatment.

摘要

成视网膜细胞瘤是儿童眼内最常见的恶性肿瘤,发病率高。长链非编码 RNA(lncRNA)在成视网膜细胞瘤的进展中发挥重要作用。已经发现 lncRNA FEZF1 反义 RNA 1(FEZF1-AS1)可刺激成视网膜细胞瘤。然而,FEZF1-AS1 促进成视网膜细胞瘤进展的机制尚不清楚。在本研究中,FEZF1-AS1 在成视网膜细胞瘤组织和细胞中上调。FEZF1-AS1 的过表达增强了成视网膜细胞瘤细胞活力,促进了细胞周期,抑制了细胞凋亡。相反,FEZF1-AS1 的下调降低了细胞活力、周期,并提高了细胞凋亡。证实了 FEZF1-AS1 与 microRNA-363-3p(miR-363-3p)之间的相互作用。FEZF1-AS1 下调 miR-363-3p 并上调 PAX6。PAX6 是 miR-363-3p 的靶基因。EZF1-AS1 通过 PAX6 促进成视网膜细胞瘤细胞活力并抑制细胞凋亡。此外,我们还证明 FEZF1-AS1 在体内有助于肿瘤形成。总之,FEZF1-AS1 通过调节 miR-363-3p/PAX6 在成视网膜细胞瘤中促进生长并抑制细胞凋亡,为成视网膜细胞瘤的治疗提供了新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b904/8096736/a3e65cd2fb67/10528_2020_10026_Fig1_HTML.jpg

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