Zhang Yali, Guan Xinyu, Wang Hao, Wang Yong, Yue Dan, Chen Ruibing
Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, P.R. China.
School of Pharmaceutical Science and Technology, Health Science Platform, Tianjin University, Tianjin 300072, P.R. China.
Oncol Lett. 2020 Oct;20(4):53. doi: 10.3892/ol.2020.11914. Epub 2020 Jul 27.
Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is upregulated in numerous types of cancer, and is implicated in various cellular processes associated with cancer progression. However, the underlying molecular mechanisms by which MALAT1 regulates metastasis remain unclear. The present study investigated the expression of MALAT1 across a range of different cancer types by analyzing RNA sequencing data from The Cancer Genome Atlas database. The results indicate that the expression of MALAT1 is highly tissue-dependent and that MALAT1 is significantly overexpressed in renal clear cell carcinoma (KIRC). The biological role of MALAT1 in regulating KIRC cell migration was further investigated using molecular and cellular assays. The results demonstrate that MALAT1 regulates the expression of cofilin-1 (CFL1), potentially by regulating RNA splicing. MALAT1 knockdown decreased the expression of CFL1 at both the mRNA and protein levels, and affected cytoskeletal rearrangement by regulating the levels of F-actin via CFL1, leading to significantly decreased cellular migration. Clinical analysis confirmed a significant correlation between MALAT1 and CFL1 expression, implicating both genes as biomarkers for poor prognosis in KIRC. The present study demonstrates a novel mechanism by which MALAT1 regulates cell migration, which may be exploited to develop novel therapeutic strategies for managing renal cancer metastasis.
长链非编码RNA（lncRNA）转移相关肺腺癌转录本1（MALAT1）在多种癌症类型中表达上调，并参与了与癌症进展相关的各种细胞过程。然而，MALAT1调节转移的潜在分子机制仍不清楚。本研究通过分析癌症基因组图谱数据库中的RNA测序数据，调查了MALAT1在一系列不同癌症类型中的表达情况。结果表明，MALAT1的表达具有高度的组织依赖性，并且在肾透明细胞癌（KIRC）中显著过表达。使用分子和细胞分析方法进一步研究了MALAT1在调节KIRC细胞迁移中的生物学作用。结果表明，MALAT1可能通过调节RNA剪接来调节丝切蛋白-1（CFL1）的表达。敲低MALAT1会使CFL1在mRNA和蛋白质水平上的表达降低，并通过CFL1调节F-肌动蛋白水平来影响细胞骨架重排，从而导致细胞迁移显著减少。临床分析证实MALAT1与CFL1表达之间存在显著相关性，表明这两个基因都是KIRC预后不良的生物标志物。本研究揭示了一种MALAT1调节细胞迁移的新机制，这可能为开发治疗肾癌转移的新策略提供依据。
