LINC00973 Induces Proliferation Arrest of Drug-Treated Cancer Cells by Preventing p21 Degradation

Карпов, Д. С.; Spirin, Pavel; Zheltukhin, Andrei O.; Tutyaeva, Vera V.; Zinovieva, Olga L.; Grineva, E. N.; Matrosova, Vera A.; Krasnov, George S.; Snezhkina, Anastasiya V.; Kudryavtseva, Anna V.; Prassolov, Vladimir; Mashkova, T. D.; Лисицын, Н. А.

doi:10.3390/ijms21218322

Cited by 6 publications

(5 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The role of DDR alterations in colorectal cancer is still not fully studied. There are only a few studies on its clinical impact and no orderly study system has been established ( Chen et al, 2014 ; Lei et al, 2019 ; Sun et al, 2019 ; Karpov et al, 2020 ; Mauri et al, 2020 ; Scagliarini et al, 2020 ; Yu et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Identification and Validation of a Novel DNA Damage and DNA Repair Related Genes Based Signature for Colon Cancer Prognosis

Wang

et al. 2021

Front. Genet.

View full text Add to dashboard Cite

Backgrounds: Colorectal cancer (CRC) with high incidence, has the third highest mortality of tumors. DNA damage and repair influence a variety of tumors. However, the role of these genes in colon cancer prognosis has been less systematically investigated. Here, we aim to establish a corresponding prognostic signature providing new therapeutic opportunities for CRC.Method: After related genes were collected from GSEA, univariate Cox regression was performed to evaluate each gene’s prognostic relevance through the TCGA-COAD dataset. Stepwise COX regression was used to establish a risk prediction model through the training sets randomly separated from the TCGA cohort and validated in the remaining testing sets and two GEO datasets (GSE17538 and GSE38832). A 12-DNA-damage-and-repair-related gene-based signature able to classify COAD patients into high and low-risk groups was developed. The predictive ability of the risk model or nomogram were evaluated by different bioinformatics‐ methods. Gene functional enrichment analysis was performed to analyze the co-expressed genes of the risk-based genes.Result: A 12-gene based prognostic signature established within 160 significant survival-related genes from DNA damage and repair related gene sets performed well with an AUC of ROC 0.80 for 5 years in the TCGA-CODA dataset. The signature includes CCNB3, ISY1, CDC25C, SMC1B, MC1R, LSP1P4, RIN2, TPM1, ELL3, POLG, CD36, and NEK4. Kaplan-Meier survival curves showed that the prognosis of the risk status owns more significant differences than T, M, N, and stage prognostic parameters. A nomogram was constructed by LASSO regression analysis with T, M, N, age, and risk as prognostic parameters. ROC curve, C-index, Calibration analysis, and Decision Curve Analysis showed the risk module and nomogram performed best in years 1, 3, and 5. KEGG, GO, and GSEA enrichment analyses suggest the risk involved in a variety of important biological processes and well-known cancer-related pathways. These differences may be the key factors affecting the final prognosis.Conclusion: The established gene signature for CRC prognosis provides a new molecular tool for clinical evaluation of prognosis, individualized diagnosis, and treatment. Therapies based on targeted DNA damage and repair mechanisms may formulate more sensitive and potential chemotherapy regimens, thereby expanding treatment options and potentially improving the clinical outcome of CRC patients.

show abstract

Section: Introductionmentioning

confidence: 99%

Identification and Validation of a Novel DNA Damage and DNA Repair Related Genes Based Signature for Colon Cancer Prognosis

Wang

et al. 2021

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…At present, there are few reports on miR-7109-3p. One study highlights LINC00973-miR-7109-Siglec-15 function in the immune evasion of clear-cell renal cell carcinoma [26]. Nagy discovered miR-4506 was differentially expressed in adenoma compared to normal both in CRC tissue and plasma samples [27].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Sequencing Analysis of the Effect of β-Elemene on Colorectal Cancer from the lncRNA-miRNA-mRNA Perspective

Deng

Chen

Yuan³

et al. 2022

Genetics Research

View full text Add to dashboard Cite

Object. β-Elemene is an emerging antitumor Chinese medicine, but the exact mechanism of action of β-elemene in colorectal cancer (CRC) remains unclear. This study aimed to explore the mechanism of the lncRNA-miRNA-mRNA network in the process of β-elemene inhibiting CRC. Methods. RNA sequencing was performed on CRC cells from the control group (untreated) and the case group (β-elemene-treated). According to the sequencing data, we screened the differentially expressed (DE) lncRNAs, miRNAs, and mRNAs and then analyzed them by functional enrichment analyses. Through the lncRNA-miRNA-mRNA network, the key miRNAs and mRNAs involved in the process of β-elemene inhibiting CRC were further identified. Results. Totally, 607 upregulated and 599 downregulated DElncRNAs, 12 downregulated and 24 upregulated DEmiRNAs, and 3153 downregulated and 3248 upregulated DEmRNAs were identified. Through the lncRNA-miRNA-mRNA network, 3 miRNAs (miR-7109-3p, miR-4506, and miR-3182), 7 prognostic mRNAs (ALPG, DTX1, HOXD13, RIMS3, SLC16A8, SYT1, and TNNT1), and 2 key mRNAs (RIMS3 and SLC16A8) were determined to participate in the inhibitory mechanism of β-elemene in CRC. Conclusion. This study revealed for the first time that the lncRNA-miRNA-mRNA network is involved in the regulation of β-elemene in CRC, and these identified miRNAs and mRNAs could be new clinical prognostic biomarkers and therapeutic targets for CRC patients.

show abstract

“…For example, LncRNA KTN1-AS1, CASC9, ABHD11-AS1, LINC00467 could participate in the progress of NSCLC ( 20 – 23 ). Studies have reported that LINC00973 was related to cancer progression ( 18 , 19 , 24 , 25 ). The expression level of LINC00973 was upregulated in cetuximab-resistant colorectal cancer H508/CR cells.…”

Section: Discussionmentioning

confidence: 99%

“…For example, chemotherapy could upregulate the expression level of LINC00973 in normal cells and cancer cells, which might be related to the activation of DNA damage response pathways or mitotic arrest. LINC00973 could reduce p21 levels, activate cancer cell proliferation, and reduce the lethality of drugs ( 18 ). Siglec-15 was a tumor immunosuppressive molecule.…”

Section: Introductionmentioning

confidence: 99%

The Regulatory Network and Potential Role of LINC00973-miRNA-mRNA ceRNA in the Progression of Non-Small-Cell Lung Cancer

Guo

Luo

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

BackgroundThe occurrence and development of cancer could be promoted by abnormally competing endogenous RNAs (ceRNA) network. This article aims to determine the prognostic biomarker of ceRNA for non-small-cell lung cancer (NSCLC) prognosis.MethodsThe expression and clinical significance of LINC00973 in NSCLC tissues were analyzed via the The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), lnCAR, and clinical samples in Taihe Hospital. The biological functions and signaling pathways involved in target genes of ceRNA network were analyzed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Survival analysis, univariate and multivariate Cox regression analysis were used for prognostic-related mRNA.ResultsExpression of LINC00973 was increased in NSCLC tissues. High expression of LINC00973 was associated with poor prognosis of NSCLC patients. There were 15 miRNA and 238 differential mRNA in the INC00973-miRNA-mRNA ceRNA network, involving cell migration, endothelial cell proliferation, tumor growth factor (TGF)-β, cellular senescence, phosphatidylinositol 3-hydroxy kinase (PI3K)-Akt, Hippo, Rap1, mitogen-activated protein kinase (MAPK), cell cycle signaling pathway, etc. The expression levels of RTKN2, NFIX, PTX3, BMP2 and LOXL2 were independent risk factors for the poor prognosis of NSCLC patients.ConclusionsLINC00973-miRNA-mRNA ceRNA network might be the basis for determining pivotal post-translational regulatory mechanisms in the progression of NSCLC. BMP2, LOXL2, NFIX, PTX3 and RTKN2 might be valuable prognostic markers and potential therapeutic targets.

show abstract

LINC00973 Induces Proliferation Arrest of Drug-Treated Cancer Cells by Preventing p21 Degradation

Cited by 6 publications

References 38 publications

Identification and Validation of a Novel DNA Damage and DNA Repair Related Genes Based Signature for Colon Cancer Prognosis

Identification and Validation of a Novel DNA Damage and DNA Repair Related Genes Based Signature for Colon Cancer Prognosis

Transcriptome Sequencing Analysis of the Effect of β-Elemene on Colorectal Cancer from the lncRNA-miRNA-mRNA Perspective

The Regulatory Network and Potential Role of LINC00973-miRNA-mRNA ceRNA in the Progression of Non-Small-Cell Lung Cancer

Contact Info

Product

Resources

About