Transcription factor NFIC functions as a tumor suppressor in lung squamous cell carcinoma progression by modulating lncRNA CASC2

Nuclear factor I (NFI) family is emerging found playing oncogenic or tumor-suppressive potential in cancers. However, the function and underlying mechanisms of NFIC, in the progression of Lung Squamous Cell Carcinoma (LUSC) remain unclear. Therefore, this study aims to probe into the function of NFIC in the development of LUSC. In the present study, we reported that NFIC was low expressed in human LUSC tissues and cell lines. NFIC inhibited LUSC cell proliferation and promoted cell apoptosis in vitro and in vivo. Moreover, NFIC also inhibited LUSC cell migration and invasion. Furthermore, we found that there were binding sites between lncRNA cancer susceptibility candidate 2 (CASC2) and NFIC, whose relationship was confirmed by the luciferase reporter assay. The expression of CASC2 and the expression of NFIC were positively correlated, and the function of CASC2 overexpression is similar to that of NFIC overexpression, which suggested that CASC2 may play a key role in LUSC development. Our study provided a new perspective for NFIC acting as an antioncogene in LUSC tumorigenesis, and NFIC and CASC2 may serve as novel potential targets for the treatment of LUSC.核因子I（Nuclear factor I，NFI）家族在癌症中兼具致癌与抑癌潜能，相关研究正日益受到学界关注。然而，NFIC在肺鳞状细胞癌（Lung Squamous Cell Carcinoma，LUSC）发生发展中的具体功能及潜在调控机制仍未明确。为此，本研究旨在探讨NFIC在LUSC发生发展中的功能。本研究结果显示，NFIC在人类LUSC组织及细胞系中呈低表达状态。体外及体内实验均证实，NFIC可抑制LUSC细胞增殖并促进细胞凋亡。此外，NFIC还能抑制LUSC细胞的迁移与侵袭能力。进一步研究发现，长链非编码RNA癌症易感候选基因2（cancer susceptibility candidate 2，CASC2）与NFIC存在结合位点，二者的相互作用经荧光素酶报告基因实验得以验证。CASC2的表达水平与NFIC呈正相关，且CASC2过表达的生物学功能与NFIC过表达高度相似，提示CASC2可能在LUSC的发生发展中发挥关键调控作用。本研究为NFIC作为抑癌基因参与LUSC肿瘤发生提供了全新视角，同时NFIC与CASC2或可成为LUSC临床治疗的新型潜在靶点。