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长链非编码 RNA TUG1 从其靶基因 RGS1 招募 miR-29c-3p,以促进黑素瘤细胞的增殖和转移。

Long non-coding RNA TUG1 recruits miR‑29c‑3p from its target gene RGS1 to promote proliferation and metastasis of melanoma cells.

机构信息

Department of Dermatology, Xinxiang Central Hospital, Xinxiang, Henan 45300, P.R. China.

Department of Dermatology, Jiaozuo People's Hospital, Jiaozuo, Henan 454001, P.R. China.

出版信息

Int J Oncol. 2019 Apr;54(4):1317-1326. doi: 10.3892/ijo.2019.4699. Epub 2019 Jan 28.

DOI:10.3892/ijo.2019.4699
PMID:30720136
Abstract

Melanoma is an aggressive type of skin cancer, characterized by high mortality rates worldwide. Therefore, the identification of new diagnostic markers and therapeutic targets for melanoma is imperative. Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) play important roles in tumor initiation and progression. It was recently reported that the expression of lncRNA taurine upregulated 1 (TUG1) was relatively higher in cancer compared with that in normal cells, and that TUG1 promoted the progression of various cancers. However, the pattern of expression and mechanism of action of TUG1 in melanoma remain unclear. The aim of the present study was to investigate whether TUG1 expression is relatively higher in melanoma tissues and whether this expression is correlated with poor overall survival. Knockdown of TUG1 was found to suppress melanoma cell growth and metastasis and induce cell apoptosis. By contrast, the overexpression of TUG1 promoted the growth and metastasis of melanoma cells, and inhibited their apoptosis. In addition, the results of the present study indicated that TUG1 sequestered endogenous miR‑29c‑3p and that it was able to suppress its expression. Furthermore, it was observed that miR‑29c‑3p could reverse the promoting effect of TUG1 on melanoma progression, which may be associated with the positive regulation of regulator of G-protein signaling 1 (RGS1), a target gene of miR‑29c‑3p. Taken together, the data of the present study demonstrated that TUG1 promoted proliferation and invasion and suppressed apoptosis in melanoma cells by regulating miR‑29c‑3p and its target gene, RGS1. Therefore, lncRNA TUG1 appears to be a promising diagnostic marker for melanoma patients.

摘要

黑色素瘤是一种侵袭性皮肤癌,其全球死亡率较高。因此,寻找新的诊断标志物和治疗靶点对于黑色素瘤至关重要。越来越多的证据表明,长链非编码 RNA(lncRNA)在肿瘤的发生和发展中起着重要作用。最近有报道称,lncRNA 牛磺酸上调 1(TUG1)在癌症组织中的表达相对高于正常细胞,并且 TUG1 促进了各种癌症的进展。然而,TUG1 在黑色素瘤中的表达模式和作用机制尚不清楚。本研究旨在探讨 TUG1 的表达是否在黑色素瘤组织中相对较高,以及这种表达是否与总生存期较差相关。敲低 TUG1 被发现可抑制黑色素瘤细胞的生长和转移,并诱导细胞凋亡。相比之下,过表达 TUG1 促进了黑色素瘤细胞的生长和转移,并抑制了其凋亡。此外,本研究结果表明,TUG1 可隔离内源性 miR-29c-3p,并能抑制其表达。此外,还观察到 miR-29c-3p 可逆转 TUG1 对黑色素瘤进展的促进作用,这可能与 miR-29c-3p 的靶基因 G 蛋白信号调节因子 1(RGS1)的正调控有关。综上所述,本研究数据表明,TUG1 通过调节 miR-29c-3p 及其靶基因 RGS1 促进黑色素瘤细胞的增殖、侵袭和抑制凋亡。因此,lncRNA TUG1 似乎是黑色素瘤患者有前途的诊断标志物。

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