Abstract
BackgroundMetastasis associated in lung adenocarcinoma transcript-1 (MALAT-1) is overexpressed during cancer progression and promotes cell migration and invasion in many solid tumors. However, its role in ovarian cancer remains poorly understood.MethodsExpressions of MALAT-1 were detected in 37 normal ovarian tissues and 45 ovarian cancer tissues by reverse transcription polymerase chain reaction (RT-PCR). Cell proliferation was observed by CCK-8 assay; Flow cytometry was used to measure cell cycle and apoptosis; Cell migration was detected by transwell migration and invasion assay. In order to evaluate the function of MALAT-1, shRNA combined with DNA microarray and Functional enrichment analysis were performed to determine the transcriptional effects of MALAT-1 silencing in OVCAR3 cells. RNA and protein expression were measured by qRT-PCR and Western blotting, respectively.ResultsWe found that upregulation of MALAT-1 mRNA in ovarian cancer tissues and enhanced MALAT-1 expression was associated with FIGO stage. Knockdown of MALAT-1 expression in OVCAR3 cells inhibited cell proliferation, migration, and invasion, leading to G0/G1 cell cycle arrest and apoptosis. Overexpressed MALAT-1 expression in SKOV3 cells promoted cell proliferation, migration and invasion. Downregulation of MALAT-1 resulted in significant change of gene expression (at least 2-fold) in 449 genes, which regulate proliferation, cell cycle, and adhesion. As a consequence of MALAT-1 knockdown, MMP13 protein expression decreased, while the expression of MMP19 and ADAMTS1 was increased.ConclusionsThe present study found that MALAT-1 is highly expressed in ovarian tumors. MALAT-1 promotes the growth and migration of ovarian cancer cells, suggesting that MALAT-1 may be an important contributor to ovarian cancer development.
Highlights
Epithelial ovarian carcinoma (EOC) is the deadliest gynecologic malignancy, accounting for significant cancer death each year [1]. and [2]
We found that upregulation of Metastasis associated in lung adenocarcinoma transcript-1 (MALAT-1) mRNA in ovarian cancer tissues and enhanced MALAT-1 expression was associated with FIGO stage
MALAT-1 promotes the growth and migration of ovarian cancer cells, suggesting that MALAT-1 may be an important contributor to ovarian cancer development
Summary
Epithelial ovarian carcinoma (EOC) is the deadliest gynecologic malignancy, accounting for significant cancer death each year [1]. and [2]. It is widely accepted that cancer development is a result of altered gene expression and/or structural changes of protein-coding genes. Genome-wide sequencing data revealed that thousands of genes lack protein-coding capacity, while playing important roles in regulation of cell growth, survival and apoptosis, and tumorigenesis or other diseases [6]. Our research is focused on MALAT-1, originally identified in non-small cell lung cancer, is a large non-coding RNA that is closely associated with tumor metastasis and regulates the expression of various metastasis-associated genes[7]. MALAT-1 expression has been found to be up-regulated in many solid tumors, such as lung [8], liver [15], and prostate cancers [16] and has a tumor-promoting function. Metastasis associated in lung adenocarcinoma transcript-1 (MALAT-1) is overexpressed during cancer progression and promotes cell migration and invasion in many solid tumors.
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