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微小 RNA-204 通过靶向 PCNA-1 抑制人肺癌细胞的增殖、迁移和侵袭,并抑制体内肿瘤生长。

MicroRNA-204 inhibits the proliferation, migration and invasion of human lung cancer cells by targeting PCNA-1 and inhibits tumor growth in vivo.

机构信息

Department of Thoracic Surgery, Shengli Oilfield Central Hospital, Dongying, Shandong 257034, P.R. China.

出版信息

Int J Mol Med. 2019 Mar;43(3):1149-1156. doi: 10.3892/ijmm.2018.4044. Epub 2018 Dec 31.

Abstract

Lung cancer accounts for ~20% of the total cancer‑associated mortalities worldwide. Lung cancer is often diagnosed at advanced stages and is therefore difficult to treat. The biomarkers for diagnosis of lung cancer are limited and unreliable. In addition, the lack of availability of efficient chemotherapeutic agents and targets has resulted in limitations in the successful treatment of lung cancer. Previously, microRNAs (miRNA/miR) have been implicated in the onset and development of several types of cancer. The expression of miRNAs is often dysregulated in cancer cells; therefore, they are considered important therapeutic targets and agents. The present study examined the expression of miR‑204 in 4 different lung cancer cell lines and 1 normal cell line. The results revealed that miR‑204 was significantly downregulated (4‑8‑fold) in all the cancer cell lines (P<0.05). Overexpression of miR‑204 in A549 lung cancer cells inhibited the proliferative, migratory and invasive capabilities of the lung cancer cells. Furthermore, miR‑204 overexpression also induced apoptosis in the A549 lung cancer cells. Bioinformatics analysis revealed proliferating cell nuclear antigen 1 (PCNA‑1) to be a potential target of miR‑204. The reverse transcription quantitative polymerase chain reaction analysis revealed that PCNA‑1 was significantly upregulated (up to 5‑fold) in the lung cancer cells (P<0.05), and the overexpression of miR‑204 caused the downregulation of PCNA‑1 in A549 lung cancer cells. Silencing of PCNA‑1 in A549 cells exerted similar effects to that of miR‑204 overexpression on the proliferative, migratory and invasive capabilities of A549 lung cancer cells. Additionally, the suppression of miR‑204 in A549 cells transfected with Si‑PCNA‑1 did not rescue the effects of PCNA‑1 silencing on cell proliferation, migration or invasion. Conversely, the overexpression of PCNA‑1 in A549 cells transfected with miR‑204 mimics promoted the proliferation, migration and invasion of lung cancer cells. Furthermore, overexpression of miR‑204 in xenograft tumors significantly inhibited their growth. Taken together, these results indicated that miR‑204 regulates the proliferative, migratory and invasive capabilities of lung cancer cells by targeting PCNA‑1.

摘要

肺癌约占全球癌症相关死亡总数的 20%。肺癌通常在晚期诊断,因此难以治疗。用于诊断肺癌的生物标志物有限且不可靠。此外,缺乏有效的化疗药物和靶点导致肺癌的成功治疗受到限制。先前的研究表明,microRNAs(miRNA/miR)与多种类型的癌症的发生和发展有关。miRNA 的表达在癌细胞中经常失调;因此,它们被认为是重要的治疗靶点和药物。本研究检测了 miR-204 在 4 种不同肺癌细胞系和 1 种正常细胞系中的表达。结果显示,所有肺癌细胞系中 miR-204 的表达均显著下调(4-8 倍)(P<0.05)。在 A549 肺癌细胞中过表达 miR-204 抑制了肺癌细胞的增殖、迁移和侵袭能力。此外,miR-204 过表达还诱导了 A549 肺癌细胞的凋亡。生物信息学分析显示增殖细胞核抗原 1(PCNA-1)是 miR-204 的潜在靶标。逆转录定量聚合酶链反应分析显示,PCNA-1 在肺癌细胞中显著上调(高达 5 倍)(P<0.05),并且 miR-204 的过表达导致 A549 肺癌细胞中 PCNA-1 的下调。在 A549 细胞中沉默 PCNA-1 对 A549 肺癌细胞的增殖、迁移和侵袭能力产生了类似于 miR-204 过表达的相似作用。此外,在转染 Si-PCNA-1 的 A549 细胞中抑制 miR-204 并不能挽救 PCNA-1 沉默对细胞增殖、迁移或侵袭的影响。相反,在转染 miR-204 模拟物的 A549 细胞中过表达 PCNA-1 促进了肺癌细胞的增殖、迁移和侵袭。此外,过表达 miR-204 可显著抑制异种移植肿瘤的生长。综上所述,这些结果表明,miR-204 通过靶向 PCNA-1 调节肺癌细胞的增殖、迁移和侵袭能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f2/6365052/6f4bfd94f73d/IJMM-43-03-1149-g00.jpg

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