TY  - EJOU
AU  - Zhang, Hang 
AU  - Chu, Meng-Yuan 
AU  - Lv, Guohui 
AU  - Li, You-Jie 
AU  - Liu, Xuhang 
AU  - Jiao, Fei 
AU  - Yan, Yun-Fei 

TI  - RP3-340N1.2 Knockdown Suppresses Proliferation and Migration by Downregulating IL-6 in Non-Small Cell Lung Cancer
T2  - BIOCELL

PY  - 2026
VL  - 50
IS  - 1
SN  - 1667-5746

AB  -  <b>Objectives:</b> Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality, with limited understanding of lncRNA-driven mechanisms in tumor progression. This study aimed to identify differentially expressed lncRNAs in NSCLC tissues and elucidate the functional role of the significantly upregulated RP3-340N1.2 in promoting malignancy. <b>Methods:</b> RNA sequencing was used to screen dysregulated lncRNAs. RP3-340N1.2 was functionally characterized via gain/loss-of-function assays in NSCLC cells, assessing proliferation, migration, and macrophage polarization. Mechanisms of interleukin 6 (IL-6) regulation were explored using cytokine profiling, Actinomycin D assays, and RNA Immunoprecipitation (RIP) assays to study RP3-340N1.2 interactions with zinc finger CCCH-type containing 12A (ZC3H12A) and IL-6 mRNA. <b>Results:</b> RP3-340N1.2 was upregulated in NSCLC tissues and cells. Functional assays demonstrated that RP3-340N1.2 knockdown suppressed NSCLC cell proliferation/migration and reduced macrophage polarization toward tumor-associated phenotypes. Mechanistically, RP3-340N1.2 knockdown promoted IL-6 mRNA degradation, as supported by reduced IL-6 levels and accelerated mRNA decay. Further RIP assays revealed that RP3-340N1.2 interacts with ZC3H12A, an RNA-binding protein previously reported to degrade IL-6 mRNA, and that RP3-340N1.2 knockdown enhanced ZC3H12A binding to IL-6 mRNA. Consequently, RP3-340N1.2 knockdown in carcinoma cells attenuated IL-6-mediated tumor-promoting effects, including tumor cell proliferation and migration. Importantly, these effects were observed not only in a direct carcinoma cell culturing system but also when carcinoma cells were exposed to conditioned medium from co-culturing RP3-340N1.2-knockdown tumor cells and macrophages. <b>Conclusion:</b> RP3-340N1.2 drives NSCLC malignancy by stabilizing IL-6 mRNA; its inhibition offers a potential therapeutic strategy to disrupt tumor-promoting interactions.
KW  - RP3-340N1.2; interleukin 6 (IL-6); zinc finger CCCH-type containing 12A (ZC3H12A); non-small cell lung cancer; tumor associated macrophage

DO  - 10.32604/biocell.2025.068322