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hsa_circ_0101119 通过与 EIF4A3 相互作用抑制 TCEAL6 表达,促进宫颈癌的进展。

hsa_circ_0101119 facilitates the progression of cervical cancer via an interaction with EIF4A3 to inhibit TCEAL6 expression.

机构信息

Department of Gynaecology and Obstetrics, Yantai Hospital of Traditional Chinese Medicine, Yantai, Shandong 264013, P.R. China.

出版信息

Mol Med Rep. 2021 Sep;24(3). doi: 10.3892/mmr.2021.12293. Epub 2021 Jul 19.

DOI:10.3892/mmr.2021.12293
PMID:34278492
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8299197/
Abstract

Recently, circular RNAs (circRNAs/circs) have attracted increased attention due to their regulatory role in a variety of cancer types. However, the role and molecular mechanisms of circRNAs in cervical cancer (CC) remain unknown. The present study aimed to investigate the function of hsa_ circ_0101119 on CC and its potential mechanisms. The differentially expressed circRNAs associated with CC were screened out using R software, according to the database of Gene Expression Omnibus (GEO). The expression levels of hsa_circ_0101119, eukaryotic initiation factor 4A‑3 (EIF4A3) and transcription elongation factor A‑like 6 (TCEAL6) in CC cells were detected via reverse transcription‑quantitative (RT‑q)PCR, and their expression levels in CC tissues were analyzed based on the database of GEO and the Cancer Genome Atlas. Moreover, the accurate functions of hsa_circ_0101119 and TCEAL6 on the proliferation, apoptosis, migration and invasion of SiHa and HeLa cells was examined using colony formation assay, 5‑ethynyl‑20‑deoxyuridine incorporation assay, flow cytometry and Transwell assay. Next, the underlying mechanisms of hsa_circ_0101119 on CC progression were determined via bioinformatics analysis, RNA immunoprecipitation assay, RNA pull down assay, RT‑qPCR and western blotting. It was found that hsa_circ_0101119 was highly expressed in CC tissues and cells, while TCEAL6 was lowly expressed. Knockdown of hsa_circ_0101119 or TCEAL6 overexpression significantly inhibited the proliferation, migration and invasion of SiHa and HeLa cells, but facilitated apoptosis. It was also demonstrated that hsa_circ_0101119 could recruit EIF4A3 to inhibit TCEAL6 expression in CC. Furthermore, knockdown of TCEAL6 could reverse the effects of silencing hsa_circ_0101119 on the proliferation, apoptosis, migration and invasion of HeLa cells. In conclusion, the present study revealed that hsa_circ_0101119 could facilitate cell proliferation, migration and invasion, and suppress apoptosis in CC via an interaction with EIF4A3 to inhibit TCEAL6 expression, which may provide a potential therapeutic target for CC treatment.

摘要

最近,由于其在多种癌症类型中的调节作用,环状 RNA(circRNAs/circs)受到了越来越多的关注。然而,circRNAs 在宫颈癌(CC)中的作用和分子机制尚不清楚。本研究旨在探讨 hsa_circ_0101119 在 CC 中的功能及其潜在机制。根据基因表达综合数据库(GEO)筛选出与 CC 相关的差异表达 circRNAs。采用逆转录-定量(RT-q)PCR 检测 CC 细胞中 hsa_circ_0101119、真核起始因子 4A-3(EIF4A3)和转录延伸因子 A 样 6(TCEAL6)的表达水平,并根据 GEO 数据库和癌症基因组图谱分析 CC 组织中的表达水平。此外,通过集落形成实验、5-乙炔基-20-脱氧尿苷掺入实验、流式细胞术和 Transwell 实验检测 hsa_circ_0101119 和 TCEAL6 对 SiHa 和 HeLa 细胞增殖、凋亡、迁移和侵袭的准确作用。接下来,通过生物信息学分析、RNA 免疫沉淀实验、RNA 下拉实验、RT-qPCR 和 Western blot 确定 hsa_circ_0101119 对 CC 进展的潜在机制。结果发现,hsa_circ_0101119 在 CC 组织和细胞中高表达,而 TCEAL6 低表达。敲低 hsa_circ_0101119 或过表达 TCEAL6 可显著抑制 SiHa 和 HeLa 细胞的增殖、迁移和侵袭,但促进凋亡。还证实 hsa_circ_0101119 可招募 EIF4A3 抑制 CC 中 TCEAL6 的表达。此外,敲低 TCEAL6 可逆转沉默 hsa_circ_0101119 对 HeLa 细胞增殖、凋亡、迁移和侵袭的影响。综上所述,本研究揭示了 hsa_circ_0101119 通过与 EIF4A3 相互作用抑制 TCEAL6 表达,促进 CC 细胞增殖、迁移和侵袭,抑制凋亡,这可能为 CC 的治疗提供一个潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0623/8299197/a9b0d88416e0/mmr-24-03-12293-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0623/8299197/cc50967a6105/mmr-24-03-12293-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0623/8299197/f41984d1ce2e/mmr-24-03-12293-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0623/8299197/ddb68e8b9623/mmr-24-03-12293-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0623/8299197/399e87c7a679/mmr-24-03-12293-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0623/8299197/ad28cde131a4/mmr-24-03-12293-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0623/8299197/a54f0934cd89/mmr-24-03-12293-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0623/8299197/a9b0d88416e0/mmr-24-03-12293-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0623/8299197/cc50967a6105/mmr-24-03-12293-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0623/8299197/f41984d1ce2e/mmr-24-03-12293-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0623/8299197/ddb68e8b9623/mmr-24-03-12293-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0623/8299197/399e87c7a679/mmr-24-03-12293-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0623/8299197/ad28cde131a4/mmr-24-03-12293-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0623/8299197/a54f0934cd89/mmr-24-03-12293-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0623/8299197/a9b0d88416e0/mmr-24-03-12293-g06.jpg

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