Non-coding RNAs in hepatocellular carcinoma: molecular functions and pathological implications

Wong, Chun Ming; Tsang, Felice Ho‐Ching; Ng, Irene Oi–Lin

doi:10.1038/nrgastro.2017.169

Cited by 354 publications

(321 citation statements)

References 196 publications

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“…LncRNAs have been established as crucial regulators in pathogenesis, especially in malignancies [32]. In the present study, we used TCGA data to determine a landscape of differentially expressed lncRNAs in HCC, which revealed a significant upregulation of LINC00958 in HCC.…”

Section: Discussionmentioning

confidence: 95%

M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma

et al. 2020

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Background: Long non-coding RNAs (lncRNAs) possess significant regulatory functions in multiple biological and pathological processes, especially in cancer. Dysregulated lncRNAs in hepatocellular carcinoma (HCC) and their therapeutic applications remain unclear.Methods: Differentially expressed lncRNA profile in HCC was constructed using TCGA data. LINC00958 expression level was examined in HCC cell lines and tissues. Univariate and multivariate analyses were performed to demonstrate the prognostic value of LINC00958. Loss-of-function and gain-of-function experiments were used to assess the effects of LINC00958 on cell proliferation, motility, and lipogenesis. Patient-derived xenograft model was established for in vivo experiments. RNA immunoprecipitation, dual luciferase reporter, biotin-labeled miRNA pulldown, fluorescence in situ hybridization, and RNA sequencing assays were performed to elucidate the underlying molecular mechanisms. We developed a PLGA-based nanoplatform encapsulating LINC00958 siRNA and evaluated its superiority for systemic administration. Results:We identified a lipogenesis-related lncRNA, LINC00958, whose expression was upregulated in HCC cell lines and tissues. High LINC00958 level independently predicted poor overall survival. Functional assays showed that LINC00958 aggravated HCC malignant phenotypes in vitro and in vivo. Mechanistically, LINC00958 sponged miR-3619-5p to upregulate hepatoma-derived growth factor (HDGF) expression, thereby facilitating HCC lipogenesis and progression. METTL3-mediated N 6 -methyladenosine modification led to LINC00958 upregulation through stabilizing its RNA transcript. A PLGA-based nanoplatform loaded with si-LINC00958 was developed for HCC systemic administration. This novel drug delivery system was controlled release, tumor targeting, safe, and presented satisfactory antitumor efficacy.

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Section: Discussionmentioning

confidence: 95%

M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma

et al. 2020

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“…Third, RNA-Seq has a better accuracy and repeatability [9][10][11][12]. Advances in RNA-Seq have enabled the examination of HCC at high resolution [13][14][15][16][17].…”

Section: Discussionmentioning

confidence: 99%

Whole transcriptome analysis of chemically induced hepatocellular carcinoma using RNA‐sequencing analysis

et al. 2019

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RNA‐sequencing (RNA‐Seq) is a useful method to explore the molecular events in cells and tissues at the transcriptional level. However, comprehensive transcriptome analysis of hepatocarcinogenesis and progression is lacking. In this study, we aimed to characterize a dimethylnitrosamine (DEN) and carbon tetrachloride (CCl4; DEN+CCl4)‐induced hepatocellular carcinoma (HCC) mouse model by RNA‐Seq. In total, 2033 genes were up‐regulated and 841 genes were down‐regulated after DEN and CCl4 stimulation. The differentially expressed genes were highly enriched for the Gene Ontology terms oxoacid metabolic process, carboxylic acid metabolic process, and organic acid metabolic process. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the top five significantly overrepresented pathways were metabolic pathways, chemical carcinogenesis, steroid hormone biosynthesis, retinol metabolism and metabolism of xenobiotics by cytochrome P450. Moreover, a protein‐protein interaction network analysis indicated that Rous sarcoma oncogene (Src) may play a key role in DEN+CCl4‐induced HCC. These results provide a comprehensive overview of transcriptome events in DEN+CCl4‐induced HCC.

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“…MicroRNAs (miRNAs) are a subset of conserved, single-strand, small non-coding RNAs (18-24nt), which can regulate gene expression by base-pairing to the 3′-UTR of the target mRNA and subsequently changing mRNA degradation and/or translational dysfunction. 4,5 Accumulating studies have found that miRNAs are aberrantly expressed and dysfunctional in HCC. [6][7][8][9] Recently, miR-NAs have been shown to be associated with diagnosis, development, progression and prognosis of human HCC.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐301b‐3p contributes to tumour growth of human hepatocellular carcinoma by repressing vestigial like family member 4

Guo

Yao

Zhu

et al. 2019

J Cellular Molecular Medi

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Micro RNA s (mi RNA s) are key regulators in the tumour growth and metastasis of human hepatocellular carcinoma ( HCC ). Increasing evidence suggests that miR‐301b‐3p functions as a driver in various types of human cancer. However, the expression pattern of miR‐301b‐3p and its functional role as well as underlying molecular mechanism in HCC remain poorly known. Our study found that miR‐301b‐3p expression was significantly up‐regulated in HCC tissues compared to adjacent non‐tumour tissues. Clinical association analysis revealed that the high level of miR‐301b‐3p closely correlated with large tumour size and advanced tumour‐node‐metastasis stages. Importantly, the high miR‐301b‐3p level predicted a prominent poorer overall survival of HCC patients. Knockdown of miR‐301b‐3p suppressed cell proliferation, led to cell cycle arrest at G2/M phase and induced apoptosis of Huh7 and Hep3B cells. Furthermore, miR‐301b‐3p knockdown suppressed tumour growth of HCC in mice. Mechanistically, miR‐301b‐3p directly bond to 3′ UTR of vestigial like family member 4 ( VGLL 4) and negatively regulated its expression. The expression of VGLL 4 mRNA was down‐regulated and inversely correlated with miR‐301b‐3p level in HCC tissues. Notably, VGLL 4 knockdown markedly repressed cell proliferation, resulted in G2/M phase arrest and promoted apoptosis of HCC cells. Accordingly, VGLL 4 silencing rescued miR‐301b‐3p knockdown attenuated HCC cell proliferation, cell cycle progression and apoptosis resistance. Collectively, our results suggest that miR‐301b‐3p is highly expressed in HCC . miR‐301b‐3p facilitates cell proliferation, promotes cell cycle progression and inhibits apoptosis of HCC cells by repressing VGLL 4.

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Non-coding RNAs in hepatocellular carcinoma: molecular functions and pathological implications

Cited by 354 publications

References 196 publications

M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma

M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma

Whole transcriptome analysis of chemically induced hepatocellular carcinoma using RNA‐sequencing analysis

MicroRNA‐301b‐3p contributes to tumour growth of human hepatocellular carcinoma by repressing vestigial like family member 4

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