Long non-coding RNAs as critical regulators and novel targets in cervical cancer: current status and future perspectives

Ranga, Shalu; Yadav, Ritu; Chhabra, Ravindresh; Chauhan, Meenakshi; Tanwar, Mukesh; Yadav, Chetna; Kadian, Lokesh; Ahuja, Parul

doi:10.1007/s10495-023-01840-6

Cited by 7 publications

(7 citation statements)

References 179 publications

(115 reference statements)

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“…Given that protein-coding genes constitute only 2% of the human genome, non-coding RNAs (ncRNAs), which are transcripts that do not code for any protein, are considered key regulatory molecules in all cellular processes ( Ranga et al, 2023 ). Among the ncRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are potential biomarkers of PD ( Kuo et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Integrative analysis of plasma and substantia nigra in Parkinson’s disease: unraveling biomarkers and insights from the lncRNA–miRNA–mRNA ceRNA network

Chun,

Kim

2024

Front. Aging Neurosci.

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IntroductionParkinson’s disease (PD) is a rapidly growing neurological disorder characterized by diverse movement symptoms. However, the underlying causes have not been clearly identified, and accurate diagnosis is challenging. This study aimed to identify potential biomarkers suitable for PD diagnosis and present an integrative perspective on the disease.MethodsWe screened the GSE7621, GSE8397-GPL96, GSE8397-GPL97, GSE20163, and GSE20164 datasets in the NCBI GEO database to identify differentially expressed (DE) mRNAs in the substantia nigra (SN). We also screened the GSE160299 dataset from the NCBI GEO database to identify DE lncRNAs and miRNAs in plasma. We then constructed 2 lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) regulatory networks based on the ceRNA hypothesis. To understand the biological function, we performed Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology analyses for each ceRNA network. The receiver operating characteristic analyses (ROC) was used to assess ceRNA results.ResultsWe identified 7 upregulated and 29 downregulated mRNAs as common DE mRNAs in the 5 SN datasets. In the blood dataset, we identified 31 DE miRNAs (9 upregulated and 22 downregulated) and 332 DE lncRNAs (69 upregulated and 263 downregulated). Based on the determined interactions, 5 genes (P2RX7, HSPA1, SLCO4A1, RAD52, and SIRT4) appeared to be upregulated as a result of 10 lncRNAs sponging 4 miRNAs (miR-411, miR-1193, miR-301b, and miR-514a-2/3). Competing with 9 genes (ANK1, CBLN1, RGS4, SLC6A3, SYNGR3, VSNL1, DDC, KCNJ6, and SV2C) for miR-671, a total of 26 lncRNAs seemed to function as ceRNAs, influencing genes to be downregulated.DiscussionIn this study, we successfully constructed 2 novel ceRNA regulatory networks in patients with PD, including 36 lncRNAs, 5 miRNAs, and 14 mRNAs. Our results suggest that these plasma lncRNAs are involved in the pathogenesis of PD by sponging miRNAs and regulating gene expression in the SN of the brain. We propose that the upregulated and downregulated lncRNA-mediated ceRNA networks represent mechanisms of neuroinflammation and dopamine neurotransmission, respectively. Our ceRNA network, which was associated with PD, suggests the potential use of DE miRNAs and lncRNAs as body fluid diagnostic biomarkers. These findings provide an integrated view of the mechanisms underlying gene regulation and interactions in PD.

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Section: Introductionmentioning

confidence: 99%

Integrative analysis of plasma and substantia nigra in Parkinson’s disease: unraveling biomarkers and insights from the lncRNA–miRNA–mRNA ceRNA network

Chun,

Kim

2024

Front. Aging Neurosci.

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“…Cervical cancer is one of the most common cancers in the female reproductive system, originating from the cervix. It is a serious threat to women’s health and is the most prevalent tumor in 23 countries [ 1 ]. CC has an incidence rate of 604,127 new cases and 341,831 deaths in 2020 as reported by the GLOBOCAN study.…”

Section: Introductionmentioning

confidence: 99%

DNA mismatch repair system regulates the expression of PD-L1 through DNMTs in cervical cancer

Guo,

Lu,

Kong

et al. 2024

Cancer Cell Int

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Background Cervical cancer (CC) is a potential clinical application of PD-1/PD-L1 inhibitor. We aimed to study the mechanism of DNA mismatch repair (MMR) system regulating the expression of PD-L1 in CC through DNA methyltransferase (DNMTs). Methods We collected pathological specimens from 118 cases of CC to analyze the relationship between PD-L1 expression and DNMTs in different MMR states. RNA interference (RNAi) technique was used to simulate the formation of CC cell line with MMR deficiency (dMMR) state, and subcutaneous tumor formation experiment was carried out in nude mice to verify the relationship between PD-L1 expression and DNMTs in MMR state. Results The PD-L1 positive rate in 118 cases of CC was 58.47%, while the microsatellite instability (MSI) status accounted for 5.93%. There was a significant difference in the expression of PD-L1 between patients within the dMMR and MMR proficient (pMMR) groups (χ2 = 21.405, P < 0.001). Subcutaneous inoculation after infection of Siha cells led to successful tumorigenesis in nude mice, accompanied by a significant increase in the level of PD-L1 expression in the mouse tumors, while the expression level of MLH1 and MSH2 protein decreased significantly. We also found that PD-L1 expression was closely related to the expression of DNMTs. Conclusion PD-L1 is universal expressed on the surface of CC cells, dMMR status enhances the expression of PD-L1 on the surface of CC cells, dMMR states of CC are related to the demethylation status of the PD-L1 gene promoter region.

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“…LncRNA could act as competing endogenous RNA (ceRNA) to compete with cancer driver genes for microRNA (miR/miRNA) response elements [ 5 ]. According to recent studies, STARD7-AS1 has been identified as an autophagy-related lncRNA and has the potential to be an independent prognostic indicator in CC, as evidenced by the significant correlation between low STARD7-AS1 expression and poor survival outcome in patients with CC based on bioinformatics analysis (data from The Cancer Genome Atlas database) [ 6 7 8 ]. Moreover, STARD7, as the adjacent gene of STARD7-AS1, has been frequently explored in cancer development [ 9 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…Since STARD7 exerted a prominent role in various types of cancer, the function of its adjacent gene STARD7-AS1 in cancer development deserved further investigation. Despite STARD7-AS1, DBH-AS1 is also suspected as a lncRNA related to autophagy in CC [ 6 7 8 ]. DBH-AS1 has been widely investigated in various types of cancer.…”

Section: Introductionmentioning

confidence: 99%

LncRNA STARD7-AS1 suppresses cervical cancer cell proliferation while promoting autophagy by regulating miR-31-5p/TXNIP axis to inactivate the mTOR signaling

Yin,

Liu,

Gong

et al. 2024

J Gynecol Oncol

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Objective Cervical cancer (CC) is a serious gynecologic health issue for women worldwide. Long non-coding RNA (lncRNA) has been well-documented in controlling malignant behavior of various cancer cells. The role of lncRNA STARD7-AS1 in regulating CC cell proliferation and autophagy and its possible mechanism were investigated in this work. Methods RNA expression and protein levels were quantified by reverse transcription quantitative polymerase chain reaction and western blotting. The location of STARD7-AS1 in CC cells was examined using subcellular fraction assays. Cell Counting Kit-8 assays and colony forming assays were performed to measure CC cell viability and proliferation. Autophagy in CC cells was evaluated using macrophage-derived chemokine (MDC) staining and transmission electron microscopy. The binding between microRNA (miR)-31-5p and STARD7-AS1 (or thioredoxin-interacting protein [TXNIP]) was determined by performing luciferase reporter, RNA pull-down or RNA immunoprecipitation assays. Results STARD7-AS1 overexpression significantly suppressed CC cell viability and proliferation while notably inducing autophagy. STARD7-AS1 upregulated TXNIP expression via interaction with miR-31-5p. In addition, the effects of STARD7-AS1 on CC cell proliferation and autophagy were reversed by TXNIP silencing. The suppressive effect of STARD7-AS1 overexpression on phosphorylated levels of mTOR and S6K1 was countervailed by TXNIP deficiency. Conclusion In conclusion, lncRNA STARD7-AS1 inhibits CC cell proliferation and promotes cell autophagy by targeting the miR-31-5p/TXNIP axis to inactivate the mTOR signaling.

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Long non-coding RNAs as critical regulators and novel targets in cervical cancer: current status and future perspectives

Cited by 7 publications

References 179 publications

Integrative analysis of plasma and substantia nigra in Parkinson’s disease: unraveling biomarkers and insights from the lncRNA–miRNA–mRNA ceRNA network

Integrative analysis of plasma and substantia nigra in Parkinson’s disease: unraveling biomarkers and insights from the lncRNA–miRNA–mRNA ceRNA network

DNA mismatch repair system regulates the expression of PD-L1 through DNMTs in cervical cancer

LncRNA STARD7-AS1 suppresses cervical cancer cell proliferation while promoting autophagy by regulating miR-31-5p/TXNIP axis to inactivate the mTOR signaling

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