<p>Long Non-Coding RNA NEAT1 Promoted Hepatocellular Carcinoma Cell Proliferation and Reduced Apoptosis Through the Regulation of Let-7b-IGF-1R Axis</p>

Abstract

Background and aimLong non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) is abnormally expressed in various human malignancies, including hepatocellular carcinoma (HCC). Let-7b is a miRNA with the effect of a tumor suppressor gene, and its expression level in various tumor tissues is lower than that in normal tissues. Studies have found that IGF-1R can be abnormally activated in the process of hepatocyte deterioration, and the expression level of IGF-1R in HCC is significantly up-regulated. The aim of this study was to investigate the functional mechanism of NEAT1/let-7b-IGF-1R axis in HCC.MethodsThe expressions of NEAT1 and microRNA (miR)-let-7b in HCC tissues and cell lines were quantified by quantitative real-time PCR (qRT-PCR). The effect of NEAT1 on tumor growth was observed in a mice model of transplanted hepatoma. The effects of down-regulation or up-regulation of NEAT1 expression in HCC cell lines were analysed from the perspectives of cell viability and apoptosis. The binding sites of NEAT1 and miR-let-7b were predicted by biological software. The expression of the miR-let-7b target molecules IGF-1R was detected by Western blotting.ResultsThe results showed that the expressions of NEAT1 were significantly increased, while the expressions of miR-let-7b were decreased in the HCC tissues and cell lines. Additionally, it was found that the expressions of NEAT1 and miR-let-7b showed a negative correlation in HCC tissues. The mouse model experiments confirmed that the interference with NEAT1 expression inhibited the tumor growth. Meanwhile, the cell viability of HepG2/Huh7 cell lines was significantly decreased via the downregulation of NEAT1, whereas the corresponding rates of apoptosis were significantly increased. It was further proven that there was a certain negative regulatory mechanism between NEAT1 and miR-1et-7b, which was related to the expression of IGF-1R.ConclusionThe over-expression of NEAT1 could promote the proliferation of HCC cells by inhibiting the expression of the miR-let-7b regulated by IGF-1R.

RETRACTED ARTICLE: Circular RNA circ_0000517 regulates hepatocellular carcinoma development via miR-326/IGF1R axis

“…Here we confirmed IGF1R was targeted via miR-326. Moreover, we confirmed the oncogenic role of IGF1R in hepatocellular carcinoma via promoting cell proliferation, migration and invasion, which was also consistent with former works [15,30,31]. In addition, IGF1R upregulation also facilitated glycolysis in hepatocellular carcinoma, which was similar to that in mammary gland tumor and gliomas [32,33].…”

“…Insulin-like growth factor type 1 receptor (IGF1R) is a member of insulin-like growth factor system, which is aberrantly expressed in hepatocellular carcinoma [14]. Furthermore, accruing studies suggest IGF1R plays an oncogenic role in hepatocellular carcinoma [15,16]. Besides, the bioinformatics analysis predicts that miR-326 might bind with circ_0000517 and IGF1R.…”

<p>Tumor-Linked Macrophages Promote HCC Development by Mediating the CCAT1/Let-7b/HMGA2 Signaling Pathway</p>

“… 16 , 33 , 34 Remarkably, long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) has been demonstrated by Liu et al to aggravate the malignant progression of HCC by way of regulating the miR-let-7b directly. 35 In addition, CCAT1 has been demonstrated to regulate cell proliferation and migration in HCC via competitively binding to miR-let-7 in our earlier study. 21 The TAMs-Mφs supernatant was observed to aggravate the progression of HCC via upregulating the lncRNA CCAT1 and HMGA2 expression and suppressing the let-7b expression in the present study, suggesting that the TAMs-Mφs supernatant might promote the HCC process through mediating the CCAT1/let-7b/HMGA2 signaling pathway, though, further studies on the mechanism to prove this hypothesis are required.…”

<p>Long Non-Coding RNA NEAT1 Promotes the Proliferation, Migration, and Metastasis of Human Breast-Cancer Cells by Inhibiting miR-146b-5p Expression</p>

“…18 lncRNA NEAT1 can promote the growth and metastasis of tumor cells in several types of cancers, such as colorectal cancer, 19 pancreatic cancer, 20 and hepatocellular carcinoma. 21 lncRNA NEAT1 has been reported to regulate the growth and mobility of BC cells by targeting CBX7 and RTCB. 22 Also, lncRNA NEAT1 confers chemoresistance and cell "stemness" in triple-negative breast cancer (TNBC) cells.…”