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环状 RNA circ-CCT3 通过调控 miR-1287-5p/TEAD1/PTCH1/LOX 轴促进肝癌进展。

Circular RNA circ‑CCT3 promotes hepatocellular carcinoma progression by regulating the miR‑1287‑5p/TEAD1/PTCH1/LOX axis.

机构信息

Department of General Practice, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China.

Department of Computed Tomography, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, P.R. China.

出版信息

Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.12014. Epub 2021 Mar 24.

Abstract

Hepatocellular carcinoma (HCC) is characterized by a poor prognosis because of its insensitivity to radiation and chemotherapy. Recently, circular RNAs (circRNAs) have been found to serve important roles in hepatocellular carcinogenesis. circ‑CCT3, a novel circRNA, was screened from the differential tissue expression results of a circRNA microarray. Relative expression levels of circ‑CCT3 in specimens and cell lines were evaluated by reverse transcription‑quantitative PCR and the relationship between circ‑CCT3 and prognosis was analyzed by Kaplan‑Meier curves. The oncogenic role of circ‑CCT3 was confirmed in HCC cells through a cell counting kit‑8 (CCK‑8) assay, a colony formation assay, acridine orange/ethidium bromide double fluorescence staining, flow cytometry, a wound‑healing assay and a Transwell assay. Bioinformatics prediction and luciferase reporter assays validated that circ‑CCT3 facilitated HCC progression through the miR‑1287‑5p/TEA domain transcription factor 1 (TEAD1) axis. TEAD1 could then directly activate patched 1 and lysyl oxidase transcription, as analyzed by chromatin immunoprecipitation and luciferase reporter assays. The present study identified a novel circRNA, circ‑CCT3, which may be used as a potential therapeutic target for HCC.

摘要

肝细胞癌(HCC)的预后较差,因为其对放射和化学疗法不敏感。最近,发现环状 RNA(circRNA)在肝细胞癌发生中发挥重要作用。circ-CCT3 是一种新型的 circRNA,是从 circRNA 微阵列的差异组织表达结果中筛选出来的。通过逆转录-定量 PCR 评估 circ-CCT3 在标本和细胞系中的相对表达水平,并通过 Kaplan-Meier 曲线分析 circ-CCT3 与预后的关系。通过细胞计数试剂盒-8(CCK-8)测定、集落形成测定、吖啶橙/溴化乙锭双重荧光染色、流式细胞术、划痕愈合测定和 Transwell 测定,在 HCC 细胞中证实了 circ-CCT3 的致癌作用。生物信息学预测和荧光素酶报告基因测定验证了 circ-CCT3 通过 miR-1287-5p/TEA 结构域转录因子 1(TEAD1)轴促进 HCC 进展。通过染色质免疫沉淀和荧光素酶报告基因测定分析,TEAD1 可以直接激活 patched 1 和赖氨酰氧化酶转录。本研究鉴定了一种新型的 circRNA,circ-CCT3,它可能被用作 HCC 的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21e4/7986040/6a386fbdad80/mmr-23-05-12014-g00.jpg

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