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微小 RNA-142-5p 通过抑制 PTEN 诱导皮肤鳞状细胞癌的癌症干细胞样特性。

MicroRNA-142-5p induces cancer stem cell-like properties of cutaneous squamous cell carcinoma via inhibiting PTEN.

机构信息

Department of Plastic Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Department of Dermatology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

J Cell Biochem. 2018 Feb;119(2):2179-2188. doi: 10.1002/jcb.26379. Epub 2017 Oct 20.

DOI:10.1002/jcb.26379
PMID:28857248
Abstract

Cutaneous squamous cell carcinoma (cSCC) is a malignancy of keratinocyte-derived skin tumor, which is regarded as the second most common skin cancer worldwide. Accumulating evidence has established that microRNAs (miRNAs) can play a critical role in tumor initiation, progression, and metastasis including cSCC. Abnormal expression of hsa-miR-142-5p has been elaborated in various tumors. Nevertheless, its expression and function in the development of cSCC remain unclear. In our study, we found that the expression of hsa-miR-142-5p in cSCC cells were greatly overexpressed compared to human benign epidermal keratinocyte cells. Moreover, inhibited hsa-miR-142-5p can repress cSCC cell growth and induce apoptosis while upregulated hsa-miR-142-5p exhibited a reverse phenomenon. Recently, cancer stem cells (CSCs) which possess the ability of self-renewal and proliferation and are able to produce cancer cells have been widely reported. However, the correlation between hsa-miR-142-5p and CSCs in cSCC is still unknown. Interestingly, we observed that overexpressing hsa-miR-142-5p can induce CSC-like properties in cSCC via activating Wnt signaling. In addition, the luciferase reporter assay data and bioinformatics analysis demonstrated that hsa-miR-142-5p can target the 3'UTR of PTEN mRNA. Taken these together, we draw a conclusion that hsa-miR-142-5p can trigger cancer stem cell-like properties of cSCC through inhibition of PTEN. Our findings may provide hsa-miR-142-5p as a new therapeutic target for cSCC.

摘要

皮肤鳞状细胞癌(cSCC)是一种来源于角质细胞的皮肤肿瘤恶性肿瘤,被认为是全球第二大常见皮肤癌。越来越多的证据表明,microRNAs(miRNAs)在肿瘤的发生、发展和转移中起着关键作用,包括 cSCC。hsa-miR-142-5p 的异常表达在各种肿瘤中已有详细阐述。然而,其在 cSCC 发展中的表达和功能尚不清楚。在我们的研究中,我们发现 cSCC 细胞中的 hsa-miR-142-5p 表达水平明显高于人良性表皮角质细胞。此外,抑制 hsa-miR-142-5p 可抑制 cSCC 细胞生长并诱导细胞凋亡,而上调 hsa-miR-142-5p 则表现出相反的现象。最近,具有自我更新和增殖能力并能产生癌细胞的癌症干细胞(CSCs)已被广泛报道。然而,hsa-miR-142-5p 与 cSCC 中的 CSCs 之间的相关性仍不清楚。有趣的是,我们观察到过表达 hsa-miR-142-5p 可以通过激活 Wnt 信号诱导 cSCC 中具有 CSC 样特性。此外,荧光素酶报告基因检测数据和生物信息学分析表明,hsa-miR-142-5p 可以靶向 PTEN mRNA 的 3'UTR。综上所述,我们得出结论,hsa-miR-142-5p 通过抑制 PTEN 触发 cSCC 的癌症干细胞样特性。我们的研究结果可能为 cSCC 提供了 hsa-miR-142-5p 作为一个新的治疗靶点。

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