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Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 regulates renal cancer cell migration via cofilin-1.

ABSTRACT: 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.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC7416383 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 regulates renal cancer cell migration via cofilin-1.

Zhang Yali Y Guan Xinyu X Wang Hao H Wang Yong Y Yue Dan D Chen Ruibing R

Oncology letters 20200727 4

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 ...[more]

PMID: 32788940

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Project description:IntroductionThe early diagnosis and detection could greatly improve the clinical outcome of gastric cancer (GC) patients. However, the non-invasive biomarkers for GC detection remain to be identified.MethodWe used online databases (GEPIA, UALCAN, Kaplan-Meier plotter, TIMER, and MEXPRESS) to explore the association between H19 or metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression in tissues and the occurrence, development, prognosis, the levels of immune cell infiltration, and methylation of GC; the correlation between mRNA expression and DNA methylation levels of genes were also examined. Methylation levels of H19 or MALAT1 in peripheral blood were compared between 150 GC patients and 100 healthy controls (HCs). Predictive nomograms were constructed among female and male groups for GC diagnosis. The calibration curves, Hosmer-Lemeshow test, and decision curve analysis were also used to examine the nomograms' predictive ability and clinical values.ResultsUsing multiple online databases, we found that the mRNA expressions of H19 and MALAT1 in tissues were related to the occurrence of GC, and such expressions were associated with immune cell infiltration of GC and negatively correlated with DNA methylation levels of H19 and MALAT1. H19 gene, H19C island, and MALAT1B island, as well as 20 CpG sites were hypermethylated in peripheral blood of GC patients compared with HCs; similar results were also found in female and male groups (P < .05 for all). The combination of H19c3, H19c4, MALAT1b12, and age, as well as the combination of H19b7, H19c1, H19c5, and age in the nomograms could distinguish GC patients from HCs in the female group and male group, respectively.ConclusionWe found statistically significant hypermethylation of H19 and MALAT1 promoters in GC patients, and meaningful sensitivity and specificity of MALAT1 and H19 methylation in discriminating GC and HCs were observed in both female and male groups, which indicates that the peripheral blood-based DNA methylation of H19 and MALAT1 could act as potential non-invasive biomarkers for the diagnosis of GC.

Dataset Information

Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 regulates renal cancer cell migration via cofilin-1.

Publications

Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 regulates renal cancer cell migration via cofilin-1.

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