CircMAN1A2 promotes vasculogenic mimicry of nasopharyngeal carcinoma cells through upregulating ERBB2 via sponging miR-940

Nasopharyngeal carcinoma(NPC)is the most prevalent human primary malignancy of the head and neck,and the presence of vasculogenic mimicry(VM)renders anti-angiogenic therapy ineffective and poorly prognostic.However,the underlying mechanisms are unclear.In the present study,we used miR-940 silencing and overexpression for in vitro NPC cell EdU staining,wound healing assay and 3D cell culture assay,and in vivo xenograft mouse model and VM formation to assess miR-940 function.We found that ectopic miR-940 expression reduced NPC cell proliferation,migration and VM,as well as tumorigenesis in vivo.By bioinformatic analysis,circMAN1A2 was identified as a circRNA that binds to miR-940.Mechanistically,we confirmed that circMAN1A2 acts as a sponge for miR-940,impairs the inhibitory effect of miR-940 on target ERBB2,and then activates the PI3K/AKT/mTOR signaling pathway using RNA-FISH,dual luciferase reporter gene and rescue analysis assays.In addition,upregulation of ERBB2 expression is associated with clinical staging and poor prognosis of NPC.Taken together,the present findings suggest that circMAN1A2 promotes VM formation and progression of NPC through miR-940/ERBB2 axis and further activates the PI3K/AKT/mTOR pathway.Therefore,circMAN1A2 may become a biomarker and therapeutic target for anti-angiogenic therapy in patients with nasopharyngeal carcinoma.

TNF-α诱导的circMAN1A2促进宫颈癌细胞的迁移、侵袭和增殖

目的:探讨肿瘤坏死因子(TNF)-α诱导的circMAN1A2对宫颈癌细胞恶性行为的影响。方法:RNA高通量测序检测TNF-α处理后人宫颈癌HeLa细胞中circRNA的表达差异性。RT-qPCR方法验证TNF-α对circMAN1A2的影响。RNase R耐受性实验验证circMAN1A2是否耐受RNase R消化。核质RNA分离实验研究circMAN1A2在HeLa细胞的定位;Transwell迁移侵袭实验、MTT实验、集落形成实验研究circMAN1A2对宫颈癌细胞恶性行为的影响。结果:RNA高通量测序检测到98种表达上调和63种表达下调的circRNA。TNF-α处理后circMAN1A2表达上调,其能够耐受RNase R消化,主要定位于HeLa细胞胞核中。细胞功能实验表明circMAN1A2能够促进宫颈癌细胞的迁移、侵袭和增殖。结论:TNF-α诱导的circMAN1A2促进宫颈癌细胞的迁移、侵袭和增殖。