BACKGROUND Circular RNA (circRNA) has been proven to play a significant role in multiple types of cancer. However, the expression and role of circRNAs in epithelial ovarian cancer (EOC) remains elusive. METHODS CircRNA and mRNA expression profiles of EOC were screened with sequencing analysis. Gene silencing and over-expression were used to study circRNA function. Cell proliferation and Matrigel invasion assays were used to detect cell proliferation and invasion, respectively. The expression of circRNAs, mRNAs and miRNAs was detected using qPCR. The location of circRNAs was detected using FISH. The expression of proteins was detected using western blot and immunohistochemistry. RESULTS CircMUC16 had increased expression in EOC tissues as compared to healthy ovarian tissues. The expression of circMUC16 was linked to the progression in stage and grade of EOC. Hence, silencing circMUC16 suppressed autophagy flux of SKOV3 cells. In contrast, ectopic expression of circMUC16 promoted autophagy flux of A2780 cells. CircMUC16-mediated autophagy exacerbated EOC invasion and metastasis. Mechanistically, circMUC16 could directly bind to miR-199a-5p and relieve suppression of target Beclin1 and RUNX1. In turn, RUNX1 elevated the expression of circMUC16 via promotion of its transcription. CircMUC16 could directly bind to ATG13 and promote its expression. CONCLUSION This study demonstrated that circMUC16 regulated Beclin1 and RUNX1 by sponging miR-199a-5p. The data suggested that circMUC16 could be a potential target for EOC diagnosis and therapy.

中文翻译：

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CircMUC16通过与ATG13和miR-199a相互作用促进上皮性卵巢癌的自噬。

背景技术已证明环形RNA（circRNA）在多种类型的癌症中起重要作用。但是，circRNA在上皮性卵巢癌（EOC）中的表达和作用仍然难以捉摸。方法采用测序方法筛选EOC的CircRNA和mRNA表达谱。基因沉默和过表达用于研究circRNA功能。细胞增殖和基质胶侵袭试验分别用于检测细胞增殖和侵袭。使用qPCR检测circRNA，mRNA和miRNA的表达。使用FISH检测到circRNA的位置。使用蛋白质印迹和免疫组织化学检测蛋白质的表达。结果与健康卵巢组织相比，CircMUC16在EOC组织中的表达增加。circMUC16的表达与EOC的阶段和等级有关。因此，沉默circMUC16抑制SKOV3细胞的自噬通量。相反，circMUC16的异位表达促进了A2780细胞的自噬通量。CircMUC16介导的自噬加剧了EOC的侵袭和转移。从机理上讲，circMUC16可以直接与miR-199a-5p结合并减轻对靶Beclin1和RUNX1的抑制。反过来，RUNX1通过促进circMUC16的转录来提高其表达。CircMUC16可以直接与ATG13结合并促进其表达。结论这项研究证明circMUC16通过海绵miR-199a-5p调节Beclin1和RUNX1。数据表明，circMUC16可能是EOC诊断和治疗的潜在目标。相反，circMUC16的异位表达促进了A2780细胞的自噬通量。CircMUC16介导的自噬加剧了EOC的侵袭和转移。从机理上讲，circMUC16可以直接与miR-199a-5p结合并减轻对靶Beclin1和RUNX1的抑制。反过来，RUNX1通过促进circMUC16的转录来提高其表达。CircMUC16可以直接与ATG13结合并促进其表达。结论这项研究证明circMUC16通过海绵miR-199a-5p调节Beclin1和RUNX1。数据表明，circMUC16可能是EOC诊断和治疗的潜在目标。相反，circMUC16的异位表达促进了A2780细胞的自噬通量。CircMUC16介导的自噬加剧了EOC的侵袭和转移。从机理上讲，circMUC16可以直接与miR-199a-5p结合并减轻对靶Beclin1和RUNX1的抑制。反过来，RUNX1通过促进circMUC16的转录来提高其表达。CircMUC16可以直接与ATG13结合并促进其表达。结论这项研究证明circMUC16通过海绵miR-199a-5p调节Beclin1和RUNX1。数据表明，circMUC16可能是EOC诊断和治疗的潜在目标。circMUC16可以直接与miR-199a-5p结合并减轻对靶Beclin1和RUNX1的抑制。反过来，RUNX1通过促进circMUC16的转录来提高其表达。CircMUC16可以直接与ATG13结合并促进其表达。结论这项研究证明circMUC16通过海绵miR-199a-5p调节Beclin1和RUNX1。数据表明，circMUC16可能是EOC诊断和治疗的潜在目标。circMUC16可以直接与miR-199a-5p结合并减轻对靶Beclin1和RUNX1的抑制。反过来，RUNX1通过促进circMUC16的转录来提高其表达。CircMUC16可以直接与ATG13结合并促进其表达。结论这项研究证明circMUC16通过海绵miR-199a-5p调节Beclin1和RUNX1。数据表明，circMUC16可能是EOC诊断和治疗的潜在目标。