ABSTRACT

Tumorigenesis is closely related to the disorder of the cell cycle. The cell cycle progression includes the interphase (G0/G1, S, and G2 phase) and mitosis (M phase). CCND1 is a key protein that regulates the entry of the G0/G1 phase into the S phase. In our study, we found that the short form of Fas Apoptosis Inhibitory Molecule 1 (FAIM-S) could regulate the expression of CCND1 and had a tumor-suppressing role in non-small cell lung cancer (NSCLC). Overexpressing FAIM-S significantly inhibited the proliferation and cell cycle progression in NSCLC cells. Further studies demonstrated that FAIM-S could interact with IKK-α, reducing its protein stability. This effect led to the suppression of the NF-κB pathway, resulting in the decreased expression of CCND1. Thus, our study demonstrated that FAIM-S functioned as a negative regulator of the NF-κB pathway and played a tumor-suppressing role through blocking cell cycle progression in NSCLC cells.

摘要

肿瘤发生与细胞周期紊乱密切相关。细胞周期进程包括间期（G0/G1、S 和 G2 期）和有丝分裂（M 期）。CCND1是调控G0/G1期进入S期的关键蛋白。在我们的研究中，我们发现短形式的 Fas 凋亡抑制分子 1 (FAIM-S) 可以调节 CCND1 的表达，并在非小细胞肺癌 (NSCLC) 中具有肿瘤抑制作用。过表达 FAIM-S 可显着抑制 NSCLC 细胞的增殖和细胞周期进程。进一步的研究表明，FAIM-S 可以与 IKK-α 相互作用，降低其蛋白质稳定性。这种作用导致 NF-κB 通路的抑制，导致 CCND1 的表达降低。因此，