Long non-coding RNA NEAT1 promotes hepatocellular carcinoma cell proliferation through the regulation of miR-129-5p-VCP-IκB

Abstract

Long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) plays an important role in the pathogenesis and development of several types of cancer. However, the functional mechanism of NEAT1 in hepatocellular carcinoma (HCC) remains unclear. NEAT1 and microRNA (miR)-129-5p expression in HCC tissues and cell lines was quantified by means of quantitative PCR. The effects of NEAT1 expression inhibition or upregulation in HCC cell lines were analyzed in terms of cell viability and apoptosis. Biological software was used to predict the binding sites of NEAT1 and miR-129-5p. The expression of the miR-129-5p target molecules valosin-containing protein (VCP) and IκB was detected using Western blotting. The effect of NEAT1 on tumor growth was observed in mouse models of transplanted hepatoma. In the present study, it was concluded that the expression of NEAT1 was significantly increased in the HCC tissues and cell lines. Meanwhile, after downregulating NEAT1 expression in HepG2/Huh7 cell lines, the cell viability was significantly lowered, whereas the corresponding rate of apoptosis was significantly increased. Additionally, it was found that the NEAT1 and miR-129-5p expression showed a negative correlation in HCC tissues. It was further proved that there was a certain negative regulatory mechanism between NEAT1 and miR-129-5p, which was related to the expression of VCP and IκB. The mouse model experiments confirmed that the interference with NEAT1 expression inhibited tumor growth. The study concluded that the overexpression of NEAT1 inhibited the expression of miR-129-5p by regulating VCP/IκB, thereby promoting the proliferation of HCC cells. This study provides new insights into the pathogenesis of HCC, as well as identifying new target genes for diagnosis and treatment. The results provide strong evidence that upregulated NEAT1 promotes the proliferation of cancer cells in hepatocellular carcinoma (HCC) and this regulatory mechanism depends on the microRNA (miR)-129-5p-valosin-containing protein-IκB axis. The study also indicates that NEAT1 could be a potential therapeutic target for HCC.

Evaluation of serum long noncoding RNA NEAT and MiR‐129‐5p in hepatocellular carcinoma

“…30 Our study showed that there was negative significant correlation between the relative expression level of serum LNC NEAT and MiR-129-5p in HCC group (p < .0001). This was coincided previously by Fang et al 31 Several studies demonstrated the role of lncRNAs in regulating the biological role of miRNA. 32 Huibing et al found that NEAT1 has a role in renal cell carcinoma through regulation of MiR-129-5p.…”

“…Huibing et al found that NEAT1 has a role in renal cell carcinoma through regulation of MiR‐129‐5p . Also a study done by Fang et al showed that LNC NEAT1 by regulation of miR‐129‐5p‐VCP‐I k B could proliferate hepatic cancer …”

“…33 Also a study done by Fang et al showed that LNC NEAT1 by regulation of miR-129-5p-VCP-IkB could proliferate hepatic cancer. 31 T A B L E 5 Correlation between expression levels of (LNC NEAT Diagnostic performance analysis of LNC NEAT and MiR 129-5p showing their diagnostic value to differentiate between HCC patients from healthy control subjects as follows: LNC NEAT; AUC = 0.981, p < .0001, cutoff point 1.02, sensitivity 100%, specificity 88.9%. MiR129 5b; AUC = 0.997, p < .0001, cutoff point 0.43, sensitivity 100%, specificity 97.2%, which revealed that relative expression level of LNC NEAT and MiR-129-5p could be used as potential biomarkers for cancer diagnosis, prognosis, and promising tools for cancer treatment.…”

LncRNA NEAT1 Regulates Cell Viability and Invasion in Esophageal Squamous Cell Carcinoma through the miR-129/CTBP2 Axis

“…It was previously reported that NEAT1 epigenetically silenced miR-129-5p expression by promoting DNA methylation of the CpG island in the miR-129 gene in breast tumorigenesis, thus resulting in an upregulation of WNT4 expression, a target of miR-129-5p [22]. Moreover, overexpression of NEAT1 inhibited the expression of miR-129-5p in hepatocellular carcinoma by regulating its targets, namely, valosin-containing protein (VCP) and inhibitor of kappa B (I κ B) [23].…”

NEAT1 upregulates TGF‐β1 to induce hepatocellular carcinoma progression by sponging hsa‐mir‐139‐5p

“…NEAT1 is a kind of lncRNA located on chromosome 11 (11q13.1), which can play critical roles and promote various human cancers tumorigenesis (Fang, Sun, et al, ). NEAT1 can function as a vital component of nuclear paraspeckles structure (Clemson et al, ; Sasaki, Ideue, Sano, Mituyama, & Hirose, ).…”