Mao Shanshan, Wu Dongyu, Cheng Xiaozhen, Wu Jinsheng
Radiotherapy Department, The First Affiliated Hospital of Hainan Medical University, Haikou 570102, Hainan Province, P.R. China.
Department of Medical Oncology, Haikou People's Hospital, Haikou 570208, Hainan Province, P.R. China.
iScience. 2024 Apr 30;27(6):109861. doi: 10.1016/j.isci.2024.109861. eCollection 2024 Jun 21.
Circular RNAs (circRNAs) plays critical roles in non-small cell lung cancer (NSCLC) development. Herein, we illustrated the effects of circ_0007432 on malignant features of NSCLC. We found that circ_0007432 played a promoting role in NSCLC progression, lying in accelerating cell viability, migration and invasion of NSCLC cells, promoting M2 macrophage polarization, suppressing cell apoptosis of NSCLC cells, and enhancing tumor growth . Mechanistically, the interactions among circ_0007432, SRSF1, KLF12, and IL-8 were validated by RNA-binding protein immunoprecipitation (RIP), electrophoretic mobility shift assay (EMSA), RNA pull-down, dual luciferase reporter assay and chromatin immunoprecipitation (ChIP) assays. Circ_0007432 upregulated KLF12 by recruiting SRSF1. KLF12 facilitated IL-8 expression and release by binding to IL-8 promoter. Furthermore, the role of circ_0007432/SRSF1/KLF12/IL-8 axis in malignant phenotypes of tumor cells or macrophage polarization was investigated using rescue experiments. In conclusion, circ_0007432 bound with SRSF1 to stabilize KLF12 and then promote IL-8 release, thus promoting malignant behaviors of NSCLC cells and M2 macrophage polarization.
环状RNA（circRNAs）在非小细胞肺癌（NSCLC）的发展中起着关键作用。在此，我们阐述了circ_0007432对NSCLC恶性特征的影响。我们发现circ_0007432在NSCLC进展中起促进作用，表现为加速NSCLC细胞的活力、迁移和侵袭，促进M2巨噬细胞极化，抑制NSCLC细胞凋亡以及促进肿瘤生长。机制上，通过RNA结合蛋白免疫沉淀（RIP）、电泳迁移率变动分析（EMSA）、RNA下拉、双荧光素酶报告基因检测和染色质免疫沉淀（ChIP）分析验证了circ_0007432、SRSF1、KLF12和IL-8之间的相互作用。circ_0007432通过招募SRSF1上调KLF12。KLF12通过与IL-8启动子结合促进IL-8的表达和释放。此外，通过拯救实验研究了circ_0007432/SRSF1/KLF12/IL-8轴在肿瘤细胞恶性表型或巨噬细胞极化中的作用。总之，circ_0007432与SRSF1结合以稳定KLF12，进而促进IL-8释放，从而促进NSCLC细胞的恶性行为和M2巨噬细胞极化。
