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LBX2-AS1 通过海绵吸附 miR-455-5p 和 miR-491-5p 促进 E2F2 基因表达从而促进卵巢癌进展。

LBX2-AS1 promotes ovarian cancer progression by facilitating E2F2 gene expression via miR-455-5p and miR-491-5p sponging.

机构信息

Department of Gynecology, Women's Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing, China.

Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

出版信息

J Cell Mol Med. 2021 Jan;25(2):1178-1189. doi: 10.1111/jcmm.16185. Epub 2020 Dec 20.

DOI:10.1111/jcmm.16185
PMID:33342041
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7812289/
Abstract

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.

摘要

LBX2-AS1 是一种长链非编码 RNA，它促进了胃肠道癌症和肺癌的发展，但它在卵巢癌发展中的参与尚未被研究。分析了从 TCGA 卵巢癌数据库中检索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，评估了卵巢癌细胞的整体细胞生长、集落形成、迁移、侵袭、凋亡和裸鼠肿瘤形成。使用 ENCORI 平台探索 LBX2-AS1 相互作用的 microRNAs 和候选 microRNAs 的靶基因。使用荧光素酶报告基因测定和 RNA 下拉测定来验证假定的 miRNA-RNA 相互作用。卵巢癌组织标本显示 LBX2-AS1 表达水平明显高于非癌对照。高表达水平的 LBX2-AS1 与患者总生存率降低显著相关。LBX2-AS1 敲低显著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，从而抑制其功能，这两种 microRNA 通过靶向 mRNA 抑制卵巢癌细胞中 E2F2 基因的表达。转染这两种 microRNA 的抑制剂或强制表达 E2F2 可逆转 LBX2-AS1 敲低对卵巢癌细胞的作用。LBX2-AS1 是卵巢癌中一种新的促癌 lncRNA。这种 lncRNA 通过抑制 miR-455-5p 和 miR-491-5p 增加了卵巢癌细胞的细胞生长、存活、迁移、侵袭和肿瘤形成，从而释放了 E2F2 促癌基因的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/7812289/9da548c4c02d/JCMM-25-1178-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/7812289/465b24dc3001/JCMM-25-1178-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/7812289/ef68b8ceeb81/JCMM-25-1178-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/7812289/ae3b657ad89b/JCMM-25-1178-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/7812289/2409dd81763d/JCMM-25-1178-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/7812289/b76d4fca3795/JCMM-25-1178-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/7812289/9da548c4c02d/JCMM-25-1178-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/7812289/465b24dc3001/JCMM-25-1178-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/7812289/ef68b8ceeb81/JCMM-25-1178-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/7812289/ae3b657ad89b/JCMM-25-1178-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/7812289/2409dd81763d/JCMM-25-1178-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/7812289/b76d4fca3795/JCMM-25-1178-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfc3/7812289/9da548c4c02d/JCMM-25-1178-g006.jpg

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