Large-scale analyses identify a cluster of novel long noncoding RNAs as potential competitive endogenous RNAs in progression of hepatocellular carcinoma

Song, Mengjia; Zhong, Ailin; Yang, Jin-Hao; He, Junyi; Cheng, Shaoyan; Zeng, Jianxiong; Huang, Yue; Pan, Qiuzhong; Zhao, Jingjing; Zhou, Ziqi; Zhu, Qian; Tang, Yan; Chen, Hao; Yang, Chih Ping; Liu, Yuan; Mo, Xiaocong; Weng, Desheng

doi:10.18632/aging.102468

Cited by 30 publications

(25 citation statements)

References 58 publications

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“…LNC00242 was high-expressed in gastric cancer (GC) tissue regulated by LINC00242/miR-1-3p/G6PD axis [21], it may be a promising biomarker of GC [22]. Mediated by E2F1, SLC16A1-AS1 could progress bladder cancer to invasive stage [23], and sever as a new diagnostic indicator in hepatocellular carcinoma [24,25]. It has been reported that SLC25A5-AS1 functions as a suppressor in the progression of gastric cancer to regulate cellular behaviors via miR-19a-3p/PTEN/PI3K/AKT signaling pathway [26].…”

Section: Discussionmentioning

confidence: 99%

Ferroptosis-Related IncRNAs Are Prognostic Biomarker of Overall Survival in Pancreatic Cancer Patients

Chen¹,

Gao²,

Zang³

et al. 2021

Preprint

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Background: Pancreatic cancer (PC) is one of the most lethal malignancies, the mortality and morbidity of which have been increasing over the past decade. Ferroptosis, a newly identified iron-dependent pattern of cell death, can be induced by iron chelators and small lipophilic antioxidants. Nonetheless, the prognostic significance of ferroptosis-related lncRNAs in PC remains to be explicated. Methods: We obtained the lncRNA expression matrix and clinicopathological information of PC patients from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) datasets in the current study. Pearson correlation analysis was conducted to delve into the ferroptosis-related lncRNAs, and univariate Cox analysis was implemented to examine the prognostic values in PC patients. The least absolute shrinkage and selection operator Cox (LASSO-Cox) analysis was performed to establish a ferroptosis-related lncRNA prognostic marker (Fe-LPM). Furthermore, we adopted a multivariate Cox regression to establish a nomogram. Gene set enrichment analysis (GSEA) and a competing endogenous RNA (ceRNA) network were also created.Results: The eight Fe-LPM (including SLC16A1-AS1, SETBP1-DT, ZNF93-AS1, SLC25A5-AS1, AC073896.2, LINC00242, PXN-AS1 and AC036176) was confirmed, and displayed a sturdy prognostic capability in the training and validation dataset. We established a nomogram based on risk score, age, pathological T stage and primary therapy outcome. GSEA revealed that several ferroptosis-related pathways are enriched in low-risk subgroups. A ceRNA network (including 4 lncRNAs, 27 miRNAs and 57 mRNAs) was also constructed to provide us some clues for finding the potential functions of these ferroptosis-related lncRNAs in PC.Conclusion: The eight Fe-LPM can be utilized for anticipating the overall survival (OS) of PC patients, which are meaningful to guiding clinical strategies of PC.

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Section: Discussionmentioning

confidence: 99%

Ferroptosis-Related IncRNAs Are Prognostic Biomarker of Overall Survival in Pancreatic Cancer Patients

Chen¹,

Gao²,

Zang³

et al. 2021

Preprint

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“…Additionally, increasing experimental evidence supports the notion that lncRNAs function as competitive endogenous RNAs (ceRNAs), which compete for microRNA (miRNA) binding to upregulate the expression of target genes [ 14 ]. The ceRNA hypothesis has provided new insights into the function of a large amount of novel lncRNAs.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA ZFPM2-AS1 acts as a miRNA sponge and promotes cell invasion through regulation of miR-139/GDF10 in hepatocellular carcinoma

Wang

et al. 2020

J Exp Clin Cancer Res

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Background Emerging evidence has shown that dysregulated expression of long noncoding RNAs (lncRNAs) is implicated in liver hepatocellular carcinoma (HCC). However, the role and molecular mechanism of differentially expressed lncRNAs in HCC has not been fully explained. Methods The expression profiles of lncRNAs in HCC samples were derived from microarrays analysis or downloaded from The Cancer Genome Atlas (TCGA), and their correlation with prognosis and clinical characteristics were further analyzed. Silencing of lncRNA ZFPM2-AS1 was conducted to assess the effect of ZFPM2-AS1 in vitro. The miRcode and Target Scan databases were used to determine the lncRNA-miRNA-mRNA interactions. The biological functions were demonstrated by luciferase reporter assay, western blotting, PCR and rescue experiments. Results The expression level of lncRNA ZFPM2-AS1 was significantly higher in HCC tissues than in adjacent normal tissues, and higher ZFPM2-AS1 was remarkably related to poor survival. Functionally, silencing of lncRNA ZFPM2-AS1 inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro. Bioinformatics analysis based on the miRcode and TargetScan databases showed that lncRNA ZFPM2-AS1 regulated GDF10 expression by competitively binding to miR-139. miR-139 and downregulated GDF10 reversed cell phenotypes caused by lncRNA ZFPM2-AS1 by rescue analysis. Conclusions ZFPM2-AS1, an upregulated lncRNA in HCC, was associated with malignant tumor phenotypes and worse patient survival. ZFPM2-AS1 regulated the progression of HCC by acting as a competing endogenous RNA (ceRNA) to competitively bind to miR-139 and regulate GDF10 expression. Our study provides new insight into the posttranscriptional regulation mechanism of lncRNA ZFPM2-AS1 and suggests that ZFPM2-AS1/miR-139/GDF10 may act as a potential therapeutic target and prognostic biomarker for HCC.

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“…PLEKHA4 (pleckstrin homology domain containing A4) might be involved in the progression of a tumor through the Wnt pathway (61). CEACAM19 (CEA cell adhesion molecule 19), DIO3OS (DIO3 opposite strand upstream RNA), and PCAT6 (prostate cancer associated transcript 6) were verified as associated with the prognosis of different cancers, including gastric cancer, breast cancer, liver cancer, and lung cancer (62)(63)(64). KCNE5 (potassium voltage-gated channel subfamily E regulatory subunit 5) was more closely related to heart disease (65).…”

Section: Discussionmentioning

confidence: 99%

Evaluating Distribution and Prognostic Value of New Tumor-Infiltrating Lymphocytes in HCC Based on a scRNA-Seq Study With CIBERSORTx

Shen

Zhou

et al. 2020

Front. Med.

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Hepatocellular carcinoma (HCC) is a commonly diagnosed cancer with high mortality rates. The immune response plays an important role in the progression of HCC. Immunotherapies are becoming an increasingly promising tool for treating cancers. Advancements in scRNA-seq (single-cell RNA sequencing) have allowed us to identify new subsets in the immune microenvironment of HCC. Yet, distribution of these new cell types and their potential prognostic value in bulk samples from large cohorts remained unclear. This study aimed to investigate the tumor-infiltration and prognostic value of new cell subsets identified by a previous scRNA-seq study in a TCGA HCC cohort using CIBERSORTx, a machine learning method to estimate cell proportion and infer cell-type-specific gene expression profiles. We observed different distributions of tumor-infiltrating lymphocytes between tumor and normal cells. Among these, the CD4-GZMA cell subset showed association with prognosis (log-rank test, p < 0.05). We further analyzed CD4-GZMA cell specific gene expression with CIBERSORTx, and found 19 prognostic genes (univariable cox regression, p < 0.05). Finally, we applied Least absolute shrinkage and selection operator (LASSO) Cox regression to construct an immune risk score model and performed a prognostic assessment of our model in TCGA and ICGC cohorts. Taken together, the immune landscape in HCC bulk samples may be more complex than assumed, with heterogeneity and different tumor-infiltration relative to scRNA-seq results. Additionally, CD4-GZMA cells and their characteristics may yield therapeutic benefits in the immune treatment of HCC.

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Large-scale analyses identify a cluster of novel long noncoding RNAs as potential competitive endogenous RNAs in progression of hepatocellular carcinoma

Cited by 30 publications

References 58 publications

Ferroptosis-Related IncRNAs Are Prognostic Biomarker of Overall Survival in Pancreatic Cancer Patients

Ferroptosis-Related IncRNAs Are Prognostic Biomarker of Overall Survival in Pancreatic Cancer Patients

Long noncoding RNA ZFPM2-AS1 acts as a miRNA sponge and promotes cell invasion through regulation of miR-139/GDF10 in hepatocellular carcinoma

Evaluating Distribution and Prognostic Value of New Tumor-Infiltrating Lymphocytes in HCC Based on a scRNA-Seq Study With CIBERSORTx

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