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LBX2‐AS1 promotes ovarian cancer progression by facilitating E2F2 gene expression via miR‐455‐5p and miR‐491‐5p sponging
Journal of Cellular and Molecular Medicine ( IF 5.3 ) Pub Date : 2020-12-20 , DOI: 10.1111/jcmm.16185
Jian Cao 1 , Huan Wang 1 , Guangquan Liu 1 , Ranran Tang 1 , Ye Ding 1 , Pengfei Xu 1 , Huayu Wang 1 , Juan Miao 2 , Xiaoyan Gu 1 , Suping Han 2
Affiliation  

LBX2‐AS1 is a long non‐coding RNA that facilitates the development of gastrointestinal cancers and lung cancer, but its participation in ovarian cancer development remained uninvestigated. Clinical data retrieved from TCGA ovarian cancer database and the clinography of 60 ovarian cancer patients who received anti‐cancer treatment in our facility were analysed. The overall cell growth, colony formation, migration, invasion, apoptosis and tumour formation on nude mice of ovarian cancer cells were evaluated before and after lentiviral‐based LBX2‐AS1 knockdown. ENCORI platform was used to explore LBX2‐AS1‐interacting microRNAs and target genes of the candidate microRNAs. Luciferase reporter gene assay and RNA pulldown assay were used to verify the putative miRNA‐RNA interactions. Ovarian cancer tissue specimens showed significant higher LBX2‐AS1 expression levels that non‐cancerous counterparts. High expression level of LBX2‐AS1 was significantly associated with reduced overall survival of patients. LBX2‐AS1 knockdown significantly down‐regulated the cell growth, colony formation, migration, invasion and tumour formation capacity of ovarian cancer cells and increased their apoptosis in vitro. LBX2‐AS1 interacts with and thus inhibits the function of miR‐455‐5p and miR‐491‐5p, both of which restrained the expression of E2F2 gene in ovarian cancer cells via mRNA targeting. Transfection of miRNA inhibitors of these two miRNAs or forced expression of E2F2 counteracted the effect of LBX2‐AS1 knockdown on ovarian cancer cells. LBX2‐AS1 was a novel cancer‐promoting lncRNA in ovarian cancer. This lncRNA increased the cell growth, survival, migration, invasion and tumour formation of ovarian cancer cells by inhibiting miR‐455‐5p and miR‐491‐5p, thus liberating the expression of E2F2 cancer‐promoting gene.

中文翻译:

LBX2-AS1 通过 miR-455-5p 和 miR-491-5p 海绵化促进 E2F2 基因表达促进卵巢癌进展

LBX2-AS1 是一种长链非编码 RNA,可促进胃肠道癌和肺癌的发展,但其在卵巢癌发展中的作用仍未得到研究。分析了从 TCGA 卵巢癌数据库中检索到的临床数据和在我们机构接受抗癌治疗的 60 名卵巢癌患者的临床资料。在基于慢病毒的 LBX2-AS1 敲低前后,评估了卵巢癌细胞裸鼠的整体细胞生长、集落形成、迁移、侵袭、凋亡和肿瘤形成。ENCORI 平台用于探索 LBX2-AS1 相互作用的 microRNA 和候选 microRNA 的靶基因。荧光素酶报告基因分析和 RNA pulldown 分析用于验证推定的 miRNA-RNA 相互作用。卵巢癌组织标本的 LBX2-AS1 表达水平显着高于非癌组织标本。LBX2-AS1 的高表达水平与患者总生存期降低显着相关。LBX2-AS1敲低显着下调卵巢癌细胞的细胞生长、集落形成、迁移、侵袭和肿瘤形成能力,并增加其体外凋亡。LBX2-AS1 与 miR-455-5p 和 miR-491-5p 相互作用并因此抑制其功能,两者均通过 mRNA 靶向抑制卵巢癌细胞中 E2F2 基因的表达。这两种 miRNA 的 miRNA 抑制剂的转染或 E2F2 的强制表达抵消了 LBX2-AS1 敲低对卵巢癌细胞的影响。LBX2-AS1是一种新型的卵巢癌促癌lncRNA。这种 lncRNA 增加了细胞的生长,
更新日期:2021-01-19
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