背景:新发现的CircUBE2D2已被证明在多种癌症中异常上调并促进癌症进展。本研究探讨了cirUBE2D2(hsa_circ_0005728)在卵巢癌(OC)进展中的作用。
方法:CircUBE2D2,miR-885-5p,通过RT-qPCR或WB检测HMGB1。SKOV-3细胞功能(包括细胞活力,凋亡,迁移,和侵袭)使用CCK-8、流式细胞术、划痕试验,和transwell分析,分别。miR-885-5p与circUBE2D2或HMGB1之间的直接关系通过双荧光素酶报告基因和RNA下拉分析得到证实。进一步探讨了cirUBE2D2在体内肿瘤异种移植实验中的作用。
结果:OC组织和细胞系具有较高的circUBE2D2和HMGB1和较低的miR-885-5p。机械上,CircUBE2D2与miR-885-5p共享结合关系,而miR-885-5p可以直接靶向HMGB1。消除circUBE2D2或miR-885-5p诱导抑制OC细胞活性。然而,通过下调miR-885-5p或HMGB1诱导,这些功能得以缓解.此外,cirUBE2D2敲除降低肿瘤生长。
结论:CircUBE2D2通过作为miR-885-5p的ceRNA海绵来调节HMGB1的表达,从而促进控制OC细胞的增殖和迁移,抑制细胞凋亡。靶向CircUBE2D2可以作为OC的新的潜在治疗策略。
The newly discovered CircUBE2D2 has been shown to abnormally upregulate and promote cancer progression in a variety of cancers. The present study explored circUBE2D2 (hsa_circ_0005728) in Ovarian Cancer (OC) progression.
CircUBE2D2, miR-885-5p, and
HMGB1 were examined by RT-qPCR or WB. SKOV-3 cell functions (including cell viability, apoptosis, migration, and invasion) were validated using the CCK-8, flow cytometry, scratch assay, and transwell assay, respectively. The direct relationship between miR-885-5p and circUBE2D2 or
HMGB1 was confirmed by a dual-luciferase reporter and RNA pull-down analysis. circUBE2D2\'s role in vivo tumor xenograft experiment was further probed.
OC tissue and cell lines had higher circUBE2D2 and
HMGB1 and lower miR-885-5p. Mechanically, CircUBE2D2 shared a binding relation with miR-885-5p, while miR-885-5p can directly target HMGB1. Eliminating circUBE2D2 or miR-885-5p induction inhibited OC cell activities. However, these functions were relieved by down-regulating miR-885-5p or
HMGB1 induction. Furthermore, circUBE2D2 knockout reduced tumor growth.
CircUBE2D2 regulates the expression of
HMGB1 by acting as a sponge of ceRNA as miR-885-5p, thereby promoting the control of OC cell proliferation and migration and inhibiting cell apoptosis. Targeting CircUBE2D2 could serve as a new potential treatment strategy for OC.