IRF3 介导的长链非编码 RNA FTX 通过上调 miR-708-5p 进而上调 FCHSD2 促进口腔鳞状细胞癌中的细胞增殖、迁移、侵袭并抑制细胞凋亡。

IRF3-mediated lncRNA FTX promotes cell proliferation, migration, invasion and suppresses cell apoptosis in oral squamous cell carcinoma by up-regulating FCHSD2 via miR-708-5p.

机构信息

Department of Stomatology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.

出版信息

Cell Mol Biol (Noisy-le-grand). 2023 Feb 28;69(2):31-36. doi: 10.14715/cmb/2023.69.2.6.

DOI:10.14715/cmb/2023.69.2.6

PMID:37224049

Abstract

In recent years, researches into the molecular mechanisms of oral squamous cell carcinoma (OSCC) have improved greatly but effective targeted therapies remain elusive. More and more evidence has referred to long non-coding RNAs (lncRNAs) as modulators of carcinomas development. As a novel lncRNA, five prime to Xist (FTX), as reported before, is overexpressed in a variety of cancers. In the present study, we sought to unclose the impacts of FTX and its molecular mechanism in OSCC. Related gene expression levels were disclosed by qRT-PCR and we found that FTX was notably overexpressed in OSCC. The biological functions of FTX in OSCC were measured by functional assays. The results displayed that depletion of FTX hinderedOSCC cell migratory, invasive and proliferative abilities, but promoted cell apoptotic levels. The relationship among interferon regulatory factor 3 (IRF3), FTX, microRNA-708-5p (miR-708-5p) and FCH and double SH3 domains 2 (FCHSD2) was determined by several mechanism assays, from which we discovered that FTX activated by IRF3 regulated FCHSD2 expression by sponging miR-708-5p. Rescue experiments showed that FTX motivated OSCC development by modulating miR-708-5p/FCHSD2 axis. In summary, FTX was an oncogene in OSCC and might provide new insights into OSCC treatment.

摘要

近年来，口腔鳞状细胞癌（OSCC）的分子机制研究有了很大的进展，但有效的靶向治疗仍然难以实现。越来越多的证据表明，长非编码 RNA（lncRNA）是癌症发展的调节剂。作为一种新型的 lncRNA，5'端至 Xist（FTX），如前所述，在多种癌症中过度表达。在本研究中，我们试图揭示 FTX 的影响及其在 OSCC 中的分子机制。通过 qRT-PCR 揭示了相关基因的表达水平，我们发现 FTX 在 OSCC 中明显过表达。通过功能测定测量了 FTX 在 OSCC 中的生物学功能。结果显示，FTX 的缺失抑制了 OSCC 细胞的迁移、侵袭和增殖能力，但促进了细胞凋亡水平。通过几种机制测定确定了干扰素调节因子 3（IRF3）、FTX、microRNA-708-5p（miR-708-5p）和 FCH 与双 SH3 结构域 2（FCHSD2）之间的关系，从中我们发现 IRF3 激活的 FTX 通过海绵 miR-708-5p 调节 FCHSD2 表达。挽救实验表明，FTX 通过调节 miR-708-5p/FCHSD2 轴促进 OSCC 的发展。总之，FTX 是 OSCC 的致癌基因，可能为 OSCC 的治疗提供新的思路。