YY1-induced lncRNA ZFPM2-AS1 facilitates cell proliferation and invasion in small cell lung cancer via upregulating of TRAF4
Zhijun Yan, Qilian Yang, Min Xue, Sheng Wang, Weijun Hong, Xiwen Gao
Abstract
BACKGROUND: Newly identified lncRNA zinc finger protein, FOG family member 2 antisense RNA 1 (ZFPM2-AS1) is identified as an oncogenic gene. However, the role of ZFPM2-AS1 in small cell lung cancer (SCLC) is poorly comprehended. METHODS: The expression of genes in SCLC tissues and cells was measured by qRT-PCR. Colony formation, EdU, CCK-8, transwell and wound healing as well as in vivo assays revealed the function of ZFPM2-AS1 in SCLC. ChIP, luciferase reporter, RIP and RNA pull down assays demonstrated the binding relation among genes. RESULTS: ZFPM2-AS1 was significantly upregulated in SCLC tissues and cells. ZFPM2-AS1 deficiency attenuated SCLC cell proliferation, invasion and migration. In addition, ZFPM2-AS1 was transcriptionally activated by Yin Yang 1 (YY1) factor. Further, miR-3612 was confirmed as downstream miRNA of ZFPM2-AS1. Moreover, TNF receptor associated factor 4 (TRAF4) was the target gene of miR-3612 in SCLC. ZFPM2-AS1, miR-3612 and TRAF4 jointly constituted a competing endogenous RNA (ceRNA) network in SCLC. Finally, TRAF4 could countervail ZFPM2-AS1 downregulation-mediated function on SCLC cell proliferation and invasion in vitro and tumor growth in vivo. CONCLUSION: Our study elucidated the oncogenic effect of ZFPM2-AS1 in SCLC progression, indicating it may be a therapeutic target for SCLC.