Knockdown of lncRNA PVT1 inhibits the proliferation and accelerates the apoptosis of colorectal cancer cells via the miR‑761/MAPK1 axis

Abstract

Colorectal cancer (CRC) is associated with high morbidity rates. Long non-coding RNAs (lncRNAs) participate in the development of CRC. However, the potential roles of lncRNA plasmacytoma variant translocation 1 (PVT1) in CRC remain unknown. Therefore, the aim of the present study was to investigate the potential roles of PVT1 in CRC. Reverse transcription-quantitative PCR and western blot analyses were conducted to determine the mRNA and protein expression levels. The cellular behaviors were detected using 5-Ethynyl-2'-deoxyuridine, Cell Counting Kit-8 and flow cytometry assays. The interaction between PVT1 and microRNA (miR)-761 or MAPK1 was confirmed using a dual-luciferase reporter assay. Moreover, the Pearson's method was applied for correlation analysis. The results demonstrated that the expression levels of PVT1 and MAPK1 were upregulated, while miR-761 was downregulated in CRC tissues. The expression of PVT1 was positively correlated with MAPK1 and negatively correlated with miR-761. In addition, PVT1 sponged miR-761 to upregulate MAPK1 expression. It was found that the knockdown of PVT1 expression inhibited the proliferation and promoted the apoptosis of CRC cells, which was more potent in cells transfected with miR-761. The regulatory role of small interfering RNA-PVT1 on the expression of apoptosis-related genes was reduced by MAPK1. Collectively, the present results suggested that knockdown of PVT1 may inhibit the progression of CRC by regulating the miR-761/MAPK1 axis, which may provide a promising biomarker for the treatment of CRC.

Regulation of a Novel CircTRRAP/miR-761/MAP3K2 CeRNA Cascade in Inflammation, Apoptosis, and Oxidative Stress in Human AC16 Cardiomyocytes under Hypoxia Conditions

“…21) miR-761 has a crucial role in regulating cell apoptosis and tissue inflammation. 22,23) Furthermore, miR-761 is able to suppress mitochondrial fission and apoptosis in H2O2-triggered cardiomyocytes and ischemia/reperfusion mice by targeting the mitochondrial fission factor. 24) Long noncoding RNA ZFAS1 regulates hypoxia/ reoxygenation-evoked cytotoxicity in HL-1 cardiomyocytes by modulating CDIP1 expression through miR-761.…”

Long noncoding RNA H19: functions and mechanisms in regulating programmed cell death in cancer

“…Although H19 is upregulated in most tumor cells, H19 is downregulated in isolated cancer types such as nephroblastoma. Lower gene expression levels of lncRNAs H19 and miR-675 ( p < 0.05) were observed in nephroblastoma cells, followed by higher gene expression levels of TGFBI than that in normal cells [ 63 ]. H19 inhibits growth and induces morphological changes in nephroblastoma cells.…”

The probable role of retroelements in the development of Wilms’ tumor in chromosomal syndromes

“…Помимо роли онкогенов lncRNA могут также оказывать супрессорное воздействие на развитие ОВ. Примером является lncRNA H19, которая ингибирует пролиферацию и способствует апоптозу клеток нефробластомы за счет регуляции путей miR-675/ TGFBI [59].…”