The functions of lncRNAs in the HPV-negative cervical cancer compared with HPV-positive cervical cancer

Liu, Yi; Liu, Hejing; Sheng, Bo; Pan, Shuya; Wang, Zhiwei; Zhu, Xueqiong

doi:10.1007/s10495-022-01761-w

Cited by 11 publications

(6 citation statements)

References 81 publications

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“…Numerous studies have confirmed that lncRNAs such as HOTAIR were involved in a variety of biological processes, including proliferation, differentiation, apoptosis, cell migration, cell invasion, development, and immune responses. [17] In various tumor cells, the expression levels of certain specific lncRNAs will change, which is expected to be screened as markers for tumor diagnosis or potential drug targets. The expression of HOTAIR is up-regulated in gastric carcinoma, liver carcinoma, thyroid carcinoma, glioma, pancreatic ductal adenocarcinoma, cervical carcinoma, non-small cell lung carcinoma and other tumors, and has obvious correlation with tumor proliferation, invasion, metastasis and prognosis.…”

Section: Discussionmentioning

confidence: 99%

The diagnostic value of lncRNA HOTAIR for cervical carcinoma in vaginal discharge and serum

Liu

2023

Medicine

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There is a lower incidence of cervical carcinoma compared with other common carcinomas, however, the mortality rate of cervical carcinoma is higher, suggesting that the treatment and prognosis of cervical carcinoma are relatively poor. Therefore, cervical carcinoma patients urgently need to find new diagnostic markers for early detection and treatment. One hundred and fifty cervical carcinoma and 100 benign cervical disease patients from 2019 January to 2021 December in Tianjin Central Hospital of Gynecology Obstetrics were selected and 100 healthy women were as normal group. The expression of HOX transcript antisense RNA (HOTAIR) in cervical carcinoma and paracancerous tissue, serum sample was measured by realtime PCR assay. The receiver operating characteristic of HOTAIR for cervical carcinoma was analyzed. The study found that the expression level of HOTAIR in primary cervical carcinoma is closely related to tumor metastasis and prognosis. The expression level of HOTAIR in paracancerous tissue was significantly lower than that in cancer tissue, and the expression level of HOTAIR in vaginal discharge and serum was higher than that in cervical carcinoma patients which was positively correlated with tumor malignancy, meanwhile, HOTAIR was significantly reduced after surgery 3 months both in vaginal discharge and serum. In order to examine the diagnostic efficiency of HOTAIR for cervical carcinoma, we found that the area under curve of vaginal discharge was 0.9723, sensitivity was 92%, specificity was 98%, the area under curve of serum was 0.8518, sensitivity was 79%, and specificity was 94% by receiver operating characteristic analysis. The accuracy were 92.7% and 89.3% in vaginal discharge and serum via certified by cervical carcinoma and benign cervical disease patient and healthy people. The above results show that the diagnostic performance of HOTAIR in vaginal discharge is higher than that of serum, and it is expected to become a marker for cervical carcinoma diagnosis and treatment.

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Section: Discussionmentioning

confidence: 99%

The diagnostic value of lncRNA HOTAIR for cervical carcinoma in vaginal discharge and serum

Liu

2023

Medicine

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“…Viral infections can induce a persistent inflammatory response, characterized by the infiltration of immune cells and the release of pro-inflammatory cytokines, chemokines, and reactive oxygen species. This chronic inflammation may contribute to the formation of a tumor-promoting microenvironment ( Hemmat and Bannazadeh Baghi, 2019 ); HPV infection may cause epigenetic modifications, such as DNA methylation ( van den Helder et al, 2022 ), histone modifications ( Lourenço de Freitas et al, 2021 ), and non-coding RNA regulation ( Liu et al, 2022a ), which can lead to the aberrant expression of genes involved in cell cycle regulation, apoptosis, and DNA repair, thereby facilitating carcinogenesis ( Figure 1 ). HPV can disrupt the apoptotic machinery, thereby promoting the survival and proliferation of UCC ( Liu et al, 2020 ).…”

Section: Human Papillomavirus (Hpv) Infection and Etiology Of Uccmentioning

confidence: 99%

Implications of viral infections and oncogenesis in uterine cervical carcinoma etiology and pathogenesis

2023

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BackgroundUterine Cervical Carcinoma (UCC) is the most prevalent gynecological malignancy globally, with a rising incidence in recent years. Accumulating evidence indicates that specific viral infections, including human papillomavirus (HPV), Epstein-Barr virus (EBV), Hepatitis B and C viruses (HBV and HCV), and human herpesvirus (HHV), may contribute to UCC development and progression. Understanding the complex interplay between viral infections and UCC risk is crucial for developing novel preventative and therapeutic interventions.MethodsThis comprehensive review investigates the association between viral infections and UCC risk by examining the roles of various viral pathogens in UCC etiology and pathogenesis, and possible molecular mechanisms. Additionally, we evaluate current diagnostic methods and potential therapeutic strategies targeting viral infections for UCC prevention or treatment.ResultsThe prevention of UCC has been significantly advanced by the emergence of self-sampling for HPV testing as a crucial tool, allowing for early detection and intervention. However, an essential challenge in UCC prevention lies in understanding how HPV and other viral coinfections, including EBV, HBV, HCV, HHV, HIV, or their concurrent presence, may potentially contribute to UCC development. The molecular mechanisms implicated in the association between viral infections and cervical cancer development include: (1) interference of viral oncogenes with cellular regulatory proteins, resulting in uncontrolled cell proliferation and malignant transformation; (2) inactivation of tumor suppressor genes by viral proteins; (3) evasion of host immune responses by viruses; (4) induction of a persistent inflammatory response, contributing to a tumor-promoting microenvironment; (5) epigenetic modifications that lead to aberrant gene expression; (6) stimulation of angiogenesis by viruses; and (7) activation of telomerase by viral proteins, leading to cellular immortalization. Additionally, viral coinfections can also enhance oncogenic potential through synergistic interactions between viral oncoproteins, employ immune evasion strategies, contribute to chronic inflammation, modulate host cellular signaling pathways, and induce epigenetic alterations, ultimately leading to cervical carcinogenesis.ConclusionRecognizing the implications of viral oncogenes in UCC etiology and pathogenesis is vital for addressing the escalating burden of UCC. Developing innovative preventative and therapeutic interventions requires a thorough understanding of the intricate relationship between viral infections and UCC risk.

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“…The emergence of Long noncoding RNAs (lncRNAs) in the carcinogenesis has been investigated in extensive studies [22][23][24] . LncRNAs regulate progression of cancer cells via downregulating or upregulating their target genes, which may play an oncogenic or tumor suppressive role in the carcinogenesis [25] . It has been reported that LncRNAs are related to cell proliferation, metastasis, apoptosis and tumor prognosis of cervical cancer [25] .…”

Section: Disscusionmentioning

confidence: 99%

“…LncRNAs regulate progression of cancer cells via downregulating or upregulating their target genes, which may play an oncogenic or tumor suppressive role in the carcinogenesis [25] . It has been reported that LncRNAs are related to cell proliferation, metastasis, apoptosis and tumor prognosis of cervical cancer [25] . Some lncRNAs were low expressed in cervical cancer, such as lncRNA snaR [26] ,…”

Section: Disscusionmentioning

confidence: 99%

Exploration of cuproptosis-Related Long Non-Coding RNA Signature to predict the clinical outcome and Immune Microenvironment in Cervical Cancer

Wang

Zhu

Zhang

et al. 2023

Preprint

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Background Cervical cancer (CC) is the fourth most frequent cancer in women worldwide, Patients with CC, those at an advanced stage or with recurrent disease, have a poor prognosis with limited treatment options. Cuproptosis, which is regulated by mitochondrial ferredoxin 1-mediated protein lipoylation, is a newly discovered form of cell death. This study aimed to explore the potential prognostic value of cuproptosis-related lncRNAs and their relationship to immune microenvironment in cervical cancer.Methods RNA-sequencing data and clinical data of female cervical cancer patients were obtained from The Cancer Genome Atlas (TCGA), and 19 cuproptosis-related genes were obtained from cuproptosis-related studies. 304 CC patients were randomly separated into training or validation cohorts in a 1:1 ratio. Pearson correlation analysis was used to screen out the lncrnas associated with copper-copper mineralization, and correlation analysis was conducted with 711 reported cuproptosis-related lncRNAs. Univariate, LASSO and multivariate Cox regression analyses were used to construct the characteristics of cuproptosis-related lncRNAs in the training cohort, and their prognostic value was further tested in the validation cohort. Patients were divided into high-and low-risk groups based on the median risk score. Independent prognostic analyses, ROC, C-index, and nomogram were carried out to assess the prognostic value of the signature. Subsequently, lncRNAs were analyzed for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes Enrichment (KEGG), immune-related functions, and tumour mutation burden (TMB). Finally, we used tumor immune dysfunction and exclusion (TIDE) algorithms on immune escape and immunotherapy of cuproptosis-related lncRNAs for CC.Results A total of 10 cuproptosis-related lncRNAs were obtained, and patients were divided into high-and low-risk groups. We found that high-risk patients had worse overall survival (OS) and progression-free survival (PFS) and higher mortality. Independent prognostic analyses, ROC, C-index, and nomogram showed that the cuproptosis-related lncRNAs can accurately predict the prognosis of patients. The nomogram and heatmap showed a distinct distribution of the high- and low-risk cuproptosis-related lncRNAs. Enrichment analysis showed that the biological functions of lncRNAs are associated with tumor development. Tumor immune microenvironmental analyses the risk score was positively correlated with the number of M0 macrophages, and mast cell activated, negatively correlated with Dendritic cells resting, M1 macrophages, mast cell resting, T cell CD4 memory activated, T cell gamma delta and T cells CD8. we analyzed immune-related functions to evaluate the immune status of the low-risk and high-risk groups, and the results showed that HLA, cytolytic activity, inflammation-promoting, check point, T-cell co-inhibition, APC co-inhibition, APC co-stimulation, CCR, MHC-I, and type I IFN response were significantly more active in the low-risk group than in the high-risk group (p > 0.05). The results of the expression levels of immune checkpoint molecules in high-risk group and low-risk group showed that the expression levels of common immune checkpoint molecules such as PDCD1, CD274, HAVCR2, CTLA4, and TIGIT in low-risk group were all higher than those in high-risk group. In terms of TME scores, immune scores and ESTIMATE scores were higher in low-risk patients than in high-risk patients, with no difference in stromal scores between them, suggesting a higher infiltration of immune cells in the low-risk group. In addition, OS was poorer in patients with low TMB. We were surprised to find that there was a negative correlation between the TIDE and risk scores, further suggesting that high-risk patients might react more actively to immunotherapy.Conclusion We identified a novel cuproptosis-related lncRNA signature which could precisely predict the prognosis of cervical cancer patients. Cuproptosis -related lncRNAs may may provide new insights into clinical applications and immunotherapy.

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The functions of lncRNAs in the HPV-negative cervical cancer compared with HPV-positive cervical cancer

Cited by 11 publications

References 81 publications

The diagnostic value of lncRNA HOTAIR for cervical carcinoma in vaginal discharge and serum

The diagnostic value of lncRNA HOTAIR for cervical carcinoma in vaginal discharge and serum

Implications of viral infections and oncogenesis in uterine cervical carcinoma etiology and pathogenesis

Exploration of cuproptosis-Related Long Non-Coding RNA Signature to predict the clinical outcome and Immune Microenvironment in Cervical Cancer

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