E2F1-Induced lncRNA BAIAP2-AS1 Overexpression Contributes to the Malignant Progression of Hepatocellular Carcinoma via miR-361-3p/SOX4 Axis

Currently, plenty of researches have revealed that long noncoding RNAs (lncRNAs) can act as crucial roles during the progression of various tumors, including hepatocellular carcinoma (HCC). Here, we measured the expression of lncRNA BAIAP2 antisense RNA 1(BAIAP2-AS1) as well as its contribution to the developments of HCC. In this study, the expressions of BAIAP2-AS1 and SOX4 were distinctly upregulated in HCC cells and tissues, and high BAIAP2-AS1 may be a novel biomarker for HCC. E2F1 activated BAIAP2-AS1 expression. The silence of BAIAP2-AS1 inhibited the proliferation and metastasis of HepG2 and PLC5 cells. Assays for relationship verification showed that BAIAP2-AS1 regulated the expression of SOX4 and miR-361-3p. Rescue experiments further confirmed the positive interaction between miR-361-3p and BAIAP2-AS1 as well as between miR-361-3p and SOX4. Overall, BAIAP2-AS1 modulated the miR-361-3p/SOX4 axis to promote the development of HCC. Thus, our study offers a potential therapeutic target for treating HCC.

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Regulation of TREM1-Mediated Inflammation in Hepatocellular Carcinoma Cells

Reports ◽

10.3390/reports4020017 ◽

2021 ◽

Vol 4 (2) ◽

pp. 17

Author(s):

Vikrant Rai ◽

Devendra K. Agrawal

Keyword(s):

Hepatocellular Carcinoma ◽

Vitamin D ◽

Chronic Inflammation ◽

Therapeutic Target ◽

Primary Liver Cancer ◽

Migration And Invasion ◽

Potential Therapeutic Target ◽

Mediators Of Inflammation ◽

Tnf Α ◽

Hcc Cells

Hepatocellular carcinoma (HCC), accounting for more than 90% of cases of primary liver cancer, is the third most common cause of cancer-related death worldwide. Chronic inflammation precedes the development of cirrhosis and HCC. TREM (triggering receptor expressed on myeloid cell)-1 is an inflammatory marker and amplifier of inflammation that signals through PI3K and ERK1/2 to activate transcription factors, resulting in increased secretion of pro-inflammatory cytokines, causing chronic inflammation and predisposing the liver to carcinogenesis. Thus, targeting TREM-1 in HCC might be a potential therapeutic target. A low level of vitamin D has been associated with chronic inflammation and poor prognosis in HCC. Thus, we evaluated the effect of vitamin D on TREM-1 expression in the HCC cell line. Additionally, the effects of high mobility group box-1, lipopolysaccharide, and transcription factor PU.1 on the expression of TREM-1 in normal liver cells and HCC cells have been investigated in the presence and absence of vitamin D. The results showed increased expression of TREM-1 in HCC cells and with IL-6, TNF-α, LPS, and rHMGB-1 and decreased expression with calcitriol. Calcitriol also attenuated the effect of IL-6, TNF-α, LPS, and rHMGB-1 on TREM-1. Calcitriol treatment attenuated the proliferation, migration, and invasion of HCC cells. These results (in vitro) provide molecular and biochemical evidence that calcitriol significantly attenuates the expression of mediators of inflammation, and thus might be used therapeutically together with conventional treatment to delay the progression of HCC. Additionally, the negative regulation of TREM-1 by PU.1 suggests PU.1 as a potential therapeutic target.

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SPATS2, negatively regulated by miR-145-5p, promotes hepatocellular carcinoma progression through regulating cell cycle

Cell Death and Disease ◽

10.1038/s41419-020-03039-y ◽

2020 ◽

Vol 11 (10) ◽

Author(s):

Gang Dong ◽

Shanshan Zhang ◽

Shen Shen ◽

Lulu Sun ◽

Xuemei Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

G1 Arrest ◽

Poor Survival ◽

Potential Therapeutic Target ◽

Normal Tissues ◽

Proliferation And Metastasis ◽

And Function ◽

Hcc Cells

Abstract Spermatogenesis associated serine rich 2 (SPATS2) has been reported to contribute to the tumorigenesis of multiple malignancies. The molecular function of SPATS2 in hepatocellular carcinoma (HCC) is still not fully understood. In this study, we aimed to investigate the expression pattern and function roles of SPATS2 in HCC. The regulation of SPATS2 expression was also explored. We found that SPATS2 was highly expressed in HCC tissues in comparison with that in adjacent normal tissues. High expression of SPATS2 was associated with vascular invasion, advanced TNM stages, tumor multiplicity, and poor survival. Functionally, SPATS2 was found to promote the proliferation and metastasis of HCC cells both in vitro and in vivo, while knockdown of SPATS2 enhanced apoptosis and G1 arrest of HCC cells in vitro. Mechanistically, bioinformatics analysis revealed that MiR-145-5p directly targeted SPATS2 and functional rescue experiments verified that MiR-145-5p overexpression could abolish the effect of SPATS2 on the regulation of HCC malignant phenotype. Taken together, our findings suggest that SPATS2 functions as an oncogene in HCC. The MiR-145-5p/SPATS2 axis provides a novel mechanism underlying HCC progression and may serve as a potential therapeutic target for HCC.

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Upregulation of miR-124-3p by Liver X Receptor Inhibits the Growth of Hepatocellular Carcinoma Cells Via Suppressing Cyclin D1 and CDK6

Technology in Cancer Research & Treatment ◽

10.1177/1533033820967473 ◽

2020 ◽

Vol 19 ◽

pp. 153303382096747

Author(s):

Dan Zhong ◽

Xilin Lyu ◽

Xiaohong Fu ◽

Peng Xie ◽

Menggang Liu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Growth ◽

Cyclin D1 ◽

Therapeutic Target ◽

Target Genes ◽

Critical Role ◽

Liver X Receptor ◽

Potential Therapeutic Target ◽

Hcc Cells

MiR-124-3p has been identified as a novel tumor suppressor and a potential therapeutic target in hepatocellular carcinoma (HCC) through regulating its target genes. However, the upstream regulatory mechanisms of mir-124-3p in HCC has not been fully understood. The transcription factor liver X receptor (LXR) plays a critical role in suppressing the proliferation of HCC cells, but it is unclear whether LXR is involved in the regulation of mir-124-3p. In the present study, we demonstrated that the expression of mir-124-3p was positively correlated with that of LXR in HCC, and the cell growth of HCC was significantly inhibited by LXR agonists. Moreover, activation of LXR with the agonists up-regulated the expression of mir-124-3p, and in turn down-regulated cyclin D1 and cyclin-dependent kinase 6 (CDK6) expression, which are the target genes of mir-124-3p. Mechanistically, miR-124-3p mediates LXR induced inhibition of HCC cell growth and down-regulation of cyclin D1 and CDK6 expression. In vivo experiments also confirmed that LXR induced miR-124-3p expression inhibited the growth of HCC xenograft tumors, as well as cyclin D1 and CDK6 expression. Our findings revealed that miR-124-3p is a novel target gene of LXR, and regulation of the miR-124-3p-cyclin D1/CDK6 pathway by LXR plays a crucial role in the proliferation of HCC cells. LXR-miR-124-3p-cyclin D1/CDK6 pathway may be a novel potential therapeutic target for HCC treatment.

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Identification and validation of potential key long noncoding RNAs in sorafenib-resistant hepatocellular carcinoma cells

PeerJ ◽

10.7717/peerj.8624 ◽

2020 ◽

Vol 8 ◽

pp. e8624

Author(s):

Manya Wu ◽

Xiaoyun Shen ◽

Yanping Tang ◽

Caifu Zhou ◽

Haixia Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

High Throughput Sequencing ◽

Noncoding Rnas ◽

Enrichment Analysis ◽

Long Noncoding Rnas ◽

Differentially Expressed ◽

Advanced Hepatocellular Carcinoma ◽

Ontology Term ◽

Huh7 Cells ◽

Hcc Cells

As the first-line treatment, sorafenib has been used for advanced hepatocellular carcinoma (HCC), but the chemoresistance commonly restricts to the clinical efficiency. In this study, we intend to investigate the genome-wide expression pattern of long noncoding RNAs (lncRNAs) in sorafenib-resistant HCC. Herein, we identified thousands of differentially expressed lncRNAs in sorafenib-resistant HCC cells by high-throughput sequencing compared to the parental. Besides, based on GO (Gene Ontology) term enrichment analysis, these differentially expressed lncRNAs are mainly related to binding and catalytic activity and biological regulation of metabolic processes in both the sorafenib-resistant Huh7 cells (Huh7-S) and sorafenib-resistant HepG2 cells (HepG2-S) compared to the parental cells. Moreover, when analyzed by KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway, the differentially expressed genes were significantly related to the tight junction. Among them, the expression of TCONS_00284048 and TCONS_00006019 was consistently up-regulated in sorafenib-resistant HCC cell lines, whereas when either was knocked down, the sensitivity of Huh7-S and HepG2-S cells to sorafenib was increased. Taken together, our data demonstrate that the lncRNA expression profile is significantly altered in sorafenib-resistant HCC cells as well as differentially expressed lncRNAs may play crucial functions on HCC sorafenib resistance and HCC progression.

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AnnexinA7 promotes epithelial–mesenchymal transition by interacting with Sorcin and contributes to aggressiveness in hepatocellular carcinoma

Cell Death and Disease ◽

10.1038/s41419-021-04287-2 ◽

2021 ◽

Vol 12 (11) ◽

Author(s):

Fei Ling ◽

Huan Zhang ◽

Yunliang Sun ◽

Jinyi Meng ◽

Jaceline Gislaine Pires Sanches ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

High Mortality ◽

Therapeutic Target ◽

Epithelial Mesenchymal Transition ◽

Interacting Proteins ◽

Potential Therapeutic Target ◽

Mesenchymal Transition ◽

Hcc Cells

AbstractHepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and metastasis is the major cause of the high mortality of HCC. In this study, we identified that AnnexinA7 (ANXA7) and Sorcin (SRI) are overexpressed and interacting proteins in HCC tissues and cells. In vitro functional investigations revealed that the interaction between ANXA7 and SRI regulated epithelial–mesenchymal transition (EMT), and then affected migration, invasion, and proliferation in HCC cells. Furthermore overexpression/knockdown of ANXA7 was remarkably effective in promoting/inhibiting tumorigenicity and EMT in vivo. Altogether, our study unveiled a mechanism that ANXA7 promotes EMT by interacting with SRI and further contributes to the aggressiveness in HCC, which provides a novel potential therapeutic target for preventing recurrence and metastasis in HCC.

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