Whole-transcriptome and proteome analyses identify key differentially expressed mRNAs, miRNAs, lncRNAs and circRNAs associated with HCC

Xu, Feng-Qing; Jiang, Liyu; Zhao, Qingjun; Zhang, Zhibiao; Liu, Yixian; Yang, Shuangshuang; Yu, Mengdan; Chen, Huiping; Zhang, Jianying

doi:10.1038/s41388-021-01908-0

Cited by 19 publications

(25 citation statements)

References 46 publications

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“…The dual-luciferase reporter gene assay confirmed that miR-107 decreased the transcription of TPM3-WT, while the fluorescence intensity did not change significantly in the plasmid containing TPM3-MUT. This confirmed the predicted binding area in 3'UTR (Figure 5B), which is a classical kind of regulating pattern between miRNAs and mRNAs (27,28). Furthermore, the experiments revealed that miR-107 mimics limited the proliferation, invasion, and migration, but facilitated the apoptosis of ESCC cell lines.…”

Section: Mir-107 Plays An Anti-cancer Role In Escc By Inhibiting Tpm3...supporting

confidence: 81%

MiR-107 inhibits the malignant biological behavior of esophageal squamous cell carcinoma by targeting TPM3

Zhang¹,

Zhang²,

Jiang³

et al. 2022

J Gastrointest Oncol

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Background: Esophageal squamous cell carcinoma (ESCC) is a highly lethal and aggressive tumor. Our previous study revealed that tropomyosin 3 (TPM3) is up-regulated in the late stage of ESCC and promotes epithelial-mesenchymal transition (EMT) via MMP2/MMP9. However, we have not yet explored the upstream regulator of TPM3. In this study, miR-107, a microRNA molecule, was predicted as an inhibitor targeting TPM3, and in vivo and in vitro experiments confirmed this hypothesis. Methods: Western blot and fluorescence quantitative polymerase chain reaction (qPCR) were applied to analyze the expression of miR-107 and TPM3. Flow cytometry, cell counting kit-8 (CCK8) assay, woundhealing assay, colony formation assay, transwell assay, and a BALB/c nude mouse (male, 8 weeks old, 20±2 g) model were used to detect the function of miR-107 and TPM3 in ESCC. Dual-luciferase assay was used to analyze the suppressed TPM3 expression induced by miR-107. Rescue experiments were also conducted in our research. Results:The cell and nude mouse models verified that TPM3 promotes proliferation, invasion and metastasis, and inhibits apoptosis, which is the opposite effect of miR-107 in ESCC. Meanwhile, the expression of TPM3 was up-regulated in the ESCC sample and cell lines, and miR-107 was down-regulated correspondingly. Dual-luciferase detection confirmed that miR-107 decreased the expression of TPM3 by targeting the 3'-untranslated region (3'-UTR) at the end of the TPM3 transcript. Further experiments verified that TPM3 could rescue the tumor suppression effect derived from miR-107.Conclusions: MiR-107 negatively regulates TPM3 expression and plays a tumor suppression role in ESCC.

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Section: Mir-107 Plays An Anti-cancer Role In Escc By Inhibiting Tpm3...supporting

confidence: 81%

MiR-107 inhibits the malignant biological behavior of esophageal squamous cell carcinoma by targeting TPM3

Zhang¹,

Zhang²,

Jiang³

et al. 2022

J Gastrointest Oncol

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“…DLEU1 is upregulated in GBM, and its knockout inhibits GBM cell proliferation and apoptosis, while sensitizing tumor cells to temozolomide (Liu et al, 2019;. Conversely, upregulating hsa-miR-128-1-5p inhibits glioma cell proliferation and promotes apoptosis (Dahai et al, 2020), and the same miRNA has been implicated in hepatocellular carcinoma (Xu et al, 2021). The ceRNA network developed here may help guide future studies of how RBM8A contributes to GBM.…”

Section: Discussionmentioning

confidence: 86%

Molecular Insights and Prognosis Associated With RBM8A in Glioblastoma

Wei

Zou

Chen

et al. 2022

Front. Mol. Biosci.

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Background: Glioblastoma (GBM) is the most invasive brain tumors, and it is associated with high rates of recurrence and mortality. The purpose of this study was to investigate the expression of RBM8A in GBM and the potential influence of its expression on the disease.Methods: Levels of RBM8A mRNA in GBM patients and controls were examined in The Cancer Genome Atlas (TCGA), GSE16011 and GSE90604 databases. GBM samples in TCGA were divided into RBM8Ahigh and RBM8Alow groups. Differentially expressed genes (DEGs) between GBM patients and controls were identified, as were DEGs between RBM8Ahigh and RBM8Alow groups. DEGs common to both of these comparisons were analyzed for coexpression and regression analyses. In addition, we identified potential effects of RBM8A on competing endogenous RNAs, immune cell infiltration, methylation modifications, and somatic mutations.Results: RBM8A is expressed at significantly higher levels in GBM than control samples, and its level correlates with tumor purity. We identified a total of 488 mRNAs that differed between GBM and controls as well as between RBM8Ahigh and RBM8Alow groups, which enrichment analysis revealed to be associated mainly with neuroblast proliferation, and T cell immune responses. We identified 174 mRNAs that gave areas under the receiver operating characteristic curve >0.7 among coexpression module genes, of which 13 were significantly associated with overall survival of GBM patients. We integrated 11 candidate mRNAs through LASSO algorithm, then nomogram, risk score, and decision curve analyses were analyzed. We found that RBM8A may compete with DLEU1 for binding to miR-128-1-5p, and aberrant RBM8A expression was associations with tumor infiltration by immune cells. Some mRNAs associated with GBM prognosis also appear to be methylated or mutated.Conclusions: Our study strongly links RBM8A expression to GBM pathobiology and patient prognosis. The candidate mRNAs identified here may lead to therapeutic targets against the disease.

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“…In another study came to similar conclusions, researchers identified 977 proteins (DEP) and 243 DEG in HCC and found that the DEP-DEGs were mainly enriched in the spliceosome and various metabolic processes. [ 38 ] The Notch signaling pathway has been found to be significantly associated with HCC cell migration, invasion, and apoptosis [ 39 ] regulates the differentiation of macrophages into M1 to promote inflammation and antitumor activity. [ 40 ] Our results are consistent with those of the above studies, indicating that these 2 signaling pathways are closely related to the occurrence and development of liver cancer, and the regulatory relationship between key snoRNAs requires further study.…”

Section: Discussionmentioning

confidence: 99%

Identification of key snoRNAs serves as biomarkers for hepatocellular carcinoma by bioinformatics methods

Xie

Zhang

et al. 2022

Medicine

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Background: Hepatocellular carcinoma (HCC) is a common malignancy with high mortality and poor prognosis due to a lack of predictive markers. However, research on small nuclear RNAs (snoRNAs) in HCC were very little. This study aimed to identify a potential diagnostic and prognostic snoRNA signature for HCC. Methods: HCC datasets from the cancer genome atlas (TCGA) and international cancer genome consortium (ICGC) cohorts were used. Differentially expressed snoRNA (DEs) were identified using the limma package. Based on the DEs, diagnostic and prognostic models were established by the least absolute shrinkage and selection operator (LASSO) regression and COX analysis, and Kaplan–Meier (K–M) survival analysis and receiver operating characteristic (ROC) curve analysis were conducted to evaluate the efficiency of signatures. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to analyze the risk score and further explore the potential correlation between the risk groups and tumor immune status in TCGA. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine the functions of key snoRNAs. Results: We constructed a 6-snoRNAs signature which could classify patients into high- or low-risk groups and found that patients in the high-risk group had a worse prognosis than those in the low-risk group and were significantly involved in p53 processes. Tumor immune status analysis revealed that CTLA4 and PDCD1 (PD1) were highly expressed in the high-risk group, which responded to PD1 inhibitor therapy. Additionally, a 25-snoRNAs diagnostic signature was constructed with an area under the curve (AUC) of 0.933 for distinguishing HCCs from normal controls. Finally, 3 key snoRNAs (SNORA11, SNORD124, and SNORD46) were identified with both diagnostic and prognostic efficacy, some of which were closely related to the spliceosome and Notch signaling pathways. Conclusions: Our study identified 6 snoRNAs that may serve as novel prognostic models and 3 key snoRNAs with both diagnostic and prognostic efficacy for HCC.

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Whole-transcriptome and proteome analyses identify key differentially expressed mRNAs, miRNAs, lncRNAs and circRNAs associated with HCC

Cited by 19 publications

References 46 publications

MiR-107 inhibits the malignant biological behavior of esophageal squamous cell carcinoma by targeting TPM3

MiR-107 inhibits the malignant biological behavior of esophageal squamous cell carcinoma by targeting TPM3

Molecular Insights and Prognosis Associated With RBM8A in Glioblastoma

Identification of key snoRNAs serves as biomarkers for hepatocellular carcinoma by bioinformatics methods

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