Long Noncoding RNA LINC01134 Promotes Hepatocellular Carcinoma Metastasis via Activating AKT1S1 and NF-κB Signaling

Wang, Chao; Chen, Yan; Chen, Kunlun; Zhang, Lei

doi:10.3389/fcell.2020.00429

Cited by 21 publications

(24 citation statements)

References 55 publications

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“…Among these lncRNAs, RHPN1-AS1 was reported to act as an oncogene in multiple human cancers, including nonsmall cell lung cancer [19], uveal melanoma [20], and breast cancer [21]. LINC01134 and MKLN1-AS were found to promote HCC progression or metastasis by previous studies [24][25][26][27][28], suggesting that the two lncRNAs might be more specific in HCC, while NRAV and CMB9-22P13.1 were 13 BioMed Research International rarely reported as an oncogene in cancers. Similar with RHPN1-AS1, MAPKAPK5-AS1 was frequently reported to act as tumor-promoting lncRNAs in multiple cancers like thyroid cancer, colorectal cancer, glioma, lung cancer, and HCC [29][30][31][32][33].…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Screening Identifies Prognostic Long Noncoding RNAs in Hepatocellular Carcinoma

Feng

et al. 2021

BioMed Research International

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Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis. Therefore, there is an urgent call for the investigation of novel biomarkers in HCC. In the present study, we identified 6 upregulated lncRNAs in HCC, including LINC01134, RHPN1-AS1, NRAV, CMB9-22P13.1, MKLN1-AS, and MAPKAPK5-AS1. Higher expression of these lncRNAs was correlated to a more advanced cancer stage and a poorer prognosis in HCC patients. Enrichment analysis revealed that these lncRNAs played a crucial role in HCC progression, possibly through a series of cancer-related biological processes, such as cell cycle, DNA replication, histone acetyltransferase complex, fatty acid oxidation, and lipid modification. Moreover, competing endogenous RNA (ceRNA) network analysis revealed that these lncRNAs could bind to certain miRNAs to promote HCC progression. Loss-of-function assays indicated that silencing of RHPN1-AS1 significantly suppressed HCC proliferation and migration. Though further validations are still needed, these identified lncRNAs could serve as valuable potential biomarkers for HCC prognosis.

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Section: Discussionmentioning

confidence: 99%

Genome-Wide Screening Identifies Prognostic Long Noncoding RNAs in Hepatocellular Carcinoma

Feng

et al. 2021

BioMed Research International

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“…Considering that AKT1S1 was the most important component of the cigarette smoke exposure-related gene signature, here we observed signi cantly NNK-promoted AKT1S1 expression, which was accord with some reports that elevated AKT1S1 expression in cancer cells and could contribute to tumor metastasis 17,25 . AKT1S1 has been identi ed as an inhibitor of the mTOR complex 1, and can be phosphorylated by AKT, and ultimately releases mTOR complex 1; AKT1S1 phosphorylation state could predict hyperactivation of the AKT-mTOR pathway in multiple cancer cell types 9 .…”

Section: Discussionsupporting

confidence: 92%

“…Through compared the gene expression patterns in KIRC and normal kidney tissues, we found nine genes were not inconsistent with the ndings in RCC cells with NNK exposure. Next, the survival analysis indicated that cigarette smoke exposure-reduced genes ANKRD12, CYB5A, ECHDC3, DCN, HOXC10 and cigarette smoke exposure-promoted gene AKT1S1 showed the positive and negative relationship with overall survival in KIRC, which was accord with some studies that decreased ANKRD12 and CYB5A and increased AKT1S1 expression show a higher frequency of tumor metastasis and are indicators of increased risk of tumor progression [15][16][17] . Though cigarette smoke exposure-reduced DCN was found to be negative prognostic factor in KIRC, increasing evidences indicate that lack of DCN expression has been regarded as an indicator of tumor metastasis 18 .…”

Section: Discussionsupporting

confidence: 75%

Identification And Validation of A Cigarette Smoke-Related Five-Gene Signature As A Prognostic Biomarker In Kidney Renal Clear Cell Carcinoma

Huang

Wang

Tang

et al. 2021

Preprint

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Cigarette smoking greatly promotes the progression of kidney renal clear cell carcinoma (KIRC), however, the underlying molecular events has not been fully established. In this study, RCC cells were exposed to the tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, nicotine-derived nitrosamine ketone) for 120 days, and then the soft agar colony formation, wound healing and transwell assays were used to explore characteristics of RCC cells. RNA-seq was used to explore differentially expressed genes. We found that NNK promoted RCC cell growth and migration in a dose-dependent manner, and RNA-seq explored 14 differentially expressed genes. In TCGA-KIRC cohort, Lasso regression and multivariate COX regression models screened and constructed a five-gene signature containing ANKRD1, CYB5A, ECHDC3, MT1E, and AKT1S1. This novel gene signature significantly associated with TNM stage, invasion depth, metastasis, and tumor grade. Moreover, when compared with individual genes, the gene signature contained a higher hazard ratio and therefore had a more powerful value for the prognosis of KIRC. A nomogram was also developed based on clinical features and the gene signature, which showed good application. Finally, AKT1S1, the most crucial component of the gene signature, was significantly induced after NNK exposure and its related AKT-mTOR signaling pathway was dramatically activated. Our findings supported that NNK exposure would promote the KIRC progression, and the novel cigarette smoke-related five-gene signature might serve as a highly efficient biomarker to identify progression of KIRC patients, AKT1S1 might play an important role in cigarette smoke exposure-induced KIRC progression.

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“…The lncRNA is a novel kind of noncoding RNA, which is at least 200 nucleotides in length. The lncRNAs may participate in the progression of various diseases, especially malignant tumors [12][13][14][15][16][17] . The lncRNAs, as important tumor gene regulators, effect tumor biological behavior, transcriptional regulation, and post-transcriptional regulation [18][19][20][21][22] .…”

Section: Introductionmentioning

confidence: 99%

LncRNA HIF1A-AS2 accelerates malignant phenotypes of renal carcinoma by modulating miR-30a-5p/SOX4 axis as a ceRNA

et al. 2021

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Objective: Several reports have proposed that lncRNAs, as potential biomarkers, participate in the progression and growth of malignant tumors. HIF1A-AS2 is a novel lncRNA and potential biomarker, involved in the genesis and development of carcinomas. However, the molecular mechanism of HIF1A-AS2 in renal carcinoma is unclear. Methods: The relative expression levels of HIF1A-AS2 and miR-30a-5p were detected using RT-qPCR in renal carcinoma tissues and cell lines. Using loss-of-function and overexpression, the biological effects of HIF1A-AS2 and miR-30a-5p in kidney carcinoma progression were characterized. Dual luciferase reporter gene analysis and Western blot were used to detect the potential mechanism of HIF1A-AS2 in renal carcinomas. Results: HIF1A-AS2 was upregulated in kidney carcinoma tissues when compared with para-carcinoma tissues (P < 0.05). In addition, tumor size, tumor node mestastasis stage and differentiation were identified as being closely associated with HIF1A-AS2 expression (P < 0.05). Knockdown or overexpression of HIF1A-AS2 either restrained or promoted the malignant phenotype and WNT/β-catenin signaling in renal carcinoma cells (P < 0.05). MiR-30a-5p was downregulated in renal cancers and partially reversed HIF1A-AS2 functions in malignant renal tumor cells. HIF1A-AS2 acted as a microRNA sponge that actively regulated the relative expression of SOX4 in sponging miR-30a-5p and subsequently increased the malignant phenotypes of renal carcinomas. HIF1A-AS2 showed a carcinogenic effect and miR-30a-5p acted as an antagonist of the anti-oncogene effects in the pathogenesis of renal carcinomas. Conclusions:The HIF1A-AS2-miR-30a-5p-SOX4 axis was associated with the malignant progression and development of renal carcinoma. The relative expression of HIF1A-AS2 was negatively correlated with the expression of miR-30a-5p, and was closely correlated with SOX4 mRNA levels in renal cancers.

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Long Noncoding RNA LINC01134 Promotes Hepatocellular Carcinoma Metastasis via Activating AKT1S1 and NF-κB Signaling

Cited by 21 publications

References 55 publications

Genome-Wide Screening Identifies Prognostic Long Noncoding RNAs in Hepatocellular Carcinoma

Genome-Wide Screening Identifies Prognostic Long Noncoding RNAs in Hepatocellular Carcinoma

Identification And Validation of A Cigarette Smoke-Related Five-Gene Signature As A Prognostic Biomarker In Kidney Renal Clear Cell Carcinoma

LncRNA HIF1A-AS2 accelerates malignant phenotypes of renal carcinoma by modulating miR-30a-5p/SOX4 axis as a ceRNA

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