RESUMEN
The incidence and related death of hepatocellular carcinoma (HCC) have increased over the past decades. However, the molecular mechanisms underlying HCC pathogenesis are not fully understood. Long noncoding RNA (lncRNA) RP11-495P10.1 has been proven to be closely associated with the progression of prostate cancer, but its role and specific mechanism in HCC are still unknown. Here, we identify that RP11-495P10.1 is highly expressed in HCC tissues and cells and contributes to the proliferation of HCC cells. Moreover, this study demonstrates that RP11-495P10.1 affects the proliferation of HCC by negatively regulating the expression of nuclear receptor subfamily 4 group a member 3 (NR4A3). Glycometabolism reprogramming is one of the main characteristics of tumor cells. In this study, we discover that RP11-495P10.1 regulates glycometabolism reprogramming by changing the expression of pyruvate dehydrogenase kinase 1 (PDK1) and pyruvate dehydrogenase (PDH), thus contributing to the proliferation of HCC cells. Furthermore, knockdown of RP11-495P10.1 increases enrichment of H3K27Ac in the promoter of NR4A3 by promoting the activity of PDH and the production of acetyl-CoA, which leads to the increased transcription of NR4A3. Altogether, RP11-495P10.1 promotes HCC cell proliferation by regulating the reprogramming of glucose metabolism and acetylation of the NR4A3 promoter via the PDK1/PDH axis, which provides an lncRNA-oriented therapeutic strategy for the diagnosis and treatment of HCC.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , ARN Largo no Codificante , Receptores de Esteroides , Humanos , Masculino , Acetilación , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/genética , Proteínas de Unión al ADN/genética , Regulación Neoplásica de la Expresión Génica , Glucosa , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , Receptores de Hormona Tiroidea/genética , Receptores de Hormona Tiroidea/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/metabolismo , Complejo Piruvato Deshidrogenasa/metabolismoRESUMEN
Thyroid cancer (TC) has been characterized as the most common malignant malady of the endocrine system. Small nucleolar RNA host gene 7 (SNHG7) has been reported to serve as a key regulator in a large number of human cancer types, but its role in TC and the underlying regulatory mechanism have never been evaluated yet. The present study indicated that the expression of SNHG7 was markedly higher in TC cell lines. Knockdown of SNHG7 led to a suppression of TC cell progression and migration. Acyl-CoA synthetase long-chain family member 1 (ACSL1) has also been demonstrated as an oncogene in many cancers. Herein an inhibition of ACSL1 after SNHG7 knockdown was captured. Further, the suppressing effects of SNHG7 knockdown on TC cell processes were counteracted by ACSL1 overexpression. Data from online bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays validated the interaction between microRNA-449a (miR-449a) and SNHG7 or ACSL1. It was also verified that SNHG7 sequestered miR-449a and therefore elevated ACSL1 expression levels. To conclude, the current study indicated that SNHG7 promoted proliferation and migration of TC cells by sponging miR-449a and therefore upregulating ACSL1. The present study may provide more explorations about the molecular regulation mechanism of long noncoding RNAs in TC progression.
