ABSTRACT

Previous studies indicated that long non-coding RNAs (LncRNAs) were involved in the progression of multiple cancers including ovarian cancer (OV). LncRNA ELFN1-AS1 functioned as an oncogene in many cancers, but its potential roles in OV were largely unclear. In the current study, we were aimed at clarifying the biological roles and molecular mechanisms of ELFN1-AS1 in OV. We found that ELFN1-AS1 was significantly upregulated in OV tissues and cell lines. High expression of ELFN1-AS1 was associated with poor prognosis in OV patients. Knockdown of ELFN1-AS1 inhibited the proliferation, migration and invasion of SKOV3 cell lines and repressed tumor growth in xenografted ovarian models. Mechanistically, ELFN1-AS1 promoted the proliferation, migration and invasion of SKOV3 cells by sponging miR-497-3p. Additionally, CLDN4 was verified to be the target of miR-497-3p. Rescue experiments revealed that miR-497-3p inhibition could partly reverse the inhibitory effect of ELFN1-AS1 silencing on proliferation, migration and invasion of SKOV3 cell lines. Taken together, our findings indicated that ELFN1-AS1 acted as an oncogene in ovarian cancer through regulating the expression of CLDN4 by directly interacting with miR-497-3p. The results suggested that ELFN1-AS1 might act as a promising therapeutic target for OV.

摘要

先前的研究表明，长的非编码RNA（LncRNA）与包括卵巢癌（OV）在内的多种癌症的进展有关。LncRNA ELFN1-AS1在许多癌症中起癌基因的作用，但在OV中的潜在作用尚不清楚。在本研究中，我们旨在阐明ELFN1-AS1在OV中的生物学作用和分子机制。我们发现ELFN1-AS1在OV组织和细胞系中显着上调。ELFN1-AS1的高表达与OV患者的预后不良有关。敲低ELFN1-AS1抑制SKOV3细胞系的增殖，迁移和侵袭，并抑制异种移植卵巢模型中的肿瘤生长。从机理上讲，ELFN1-AS1通过使miR-497-3p海绵化来促进SKOV3细胞的增殖，迁移和侵袭。另外，CLDN4被证实是miR-497-3p的靶标。救援实验显示，miR-497-3p抑制作用可以部分逆转ELFN1-AS1沉默对SKOV3细胞系增殖，迁移和侵袭的抑制作用。综上所述，我们的发现表明ELFN1-AS1通过与miR-497-3p直接相互作用来调节CLDN4的表达，从而在卵巢癌中起着癌基因的作用。结果表明ELFN1-AS1可能作为OV的有希望的治疗靶点。我们的发现表明，ELFN1-AS1通过与miR-497-3p直接相互作用来调节CLDN4的表达，从而在卵巢癌中起着癌基因的作用。结果表明ELFN1-AS1可能作为OV的有希望的治疗靶点。我们的发现表明，ELFN1-AS1通过与miR-497-3p直接相互作用来调节CLDN4的表达，从而在卵巢癌中起着癌基因的作用。结果表明ELFN1-AS1可能作为OV的有希望的治疗靶点。