Abstract
BackgroundIncreased long noncoding RNA (lncRNA) expression is characteristic to hepatocellular carcinoma (HCC) and several other neoplasms. The present study aimed to identify the mechanism underlying modulation of HCC development by the lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1).MethodsQuantitative real-time polymerase chain reaction was used to determine MALAT1 and microRNA (miR)-146a expression in HCC tissues and cell lines. Western blotting was performed to measure PI3K, Akt, and mTOR levels. Dual-luciferase reporter assay was used to validate the direct targeting and negative regulatory interaction between miR-146a and MALAT1. Cell viability, proliferation, and apoptosis were analyzed using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, colony formation assay, and flow cytometry, respectively; autophagy was detected based on LC3B expression.ResultsMALAT1 expression was higher in HCC tissues than in normal tissues. MALAT1 upregulation promoted HCC cell proliferation, whereas MALAT1 downregulation promoted HCC apoptosis and autophagy. Moreover, effects of MALAT1 downregulation on HCC cells were abolished by miR-146a inhibition. miR-146a directly targeted the 3′-untranslated region of PI3K, and PI3K protein level was clearly decreased upon miR-146a mimic transfection.ConclusionsMALAT1 may modulate HCC cell proliferation, apoptosis, and autophagy via sponging miR-146a, which regulates HCC progression.
Highlights
Increased long noncoding RNA expression is characteristic to hepatocellular carcinoma (HCC) and several other neoplasms
The findings revealed that miR-146a mimic transfection suppressed the activity of luciferase, which was fused with the 3′-untranslated regions (UTRs) of PI3K, by 50%
metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) silencing downregulated miR-146a expression but upregulated PI3K expression, affecting the phosphorylation of downstream Akt and mTOR (Fig. 7e, f ). These results indicate that miR-146a expression was negatively regulated activation of the PI3K/Akt/mTOR axis
Summary
Increased long noncoding RNA (lncRNA) expression is characteristic to hepatocellular carcinoma (HCC) and several other neoplasms. The present study aimed to identify the mechanism underlying modulation of HCC development by the lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). Hepatocellular carcinoma (HCC) shows frequent recurrence, poor prognosis, and high associated morbidity, thereby posing a threat to public health [1, 2]. Alcoholism, aflatoxin intake, and hepatitis are the etiological factors that increase the risk of HCC development [3, 4]. HCC develops into malignancies through genetic and epigenetic variations [5]. Most patients with HCC are diagnosed at an advanced stage, when most therapies are ineffective. While molecular mechanisms of HCC have been explored in a few studies, these efforts have not translated into improvement in patient survival. There is a clinically unmet need for finding novel therapeutic targets for HCC
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