Methylation of the L1 gene and integration of human papillomavirus 16 and 18 in cervical carcinoma and premalignant lesions

Torres-Rojas, Francisco I; Alarcón‐Romero, Luz del Carmen; Leyva‐Vázquez, Marco Antonio; Ortíz-Ortíz, Julio; Mendoza-Catalán, Miguel Ángel; Hernández-Sotelo, Daniel; Moral-Hernández, Oscar Del; Rodríguez-Ruiz, Hugo Alberto; Leyva‐Illades, Dinorah; Flores‐Alfaro, Eugenia; Illades‐Aguiar, Berenice

doi:10.3892/ol.2017.7596

Cited by 12 publications

(14 citation statements)

References 59 publications

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“…Host or viral epigenetic changes may be enhanced by the integration of HPV. A recent study showed that L1 gene methylation increases significantly according to the grade of the cervical lesion, and a high methylation rate of this gene correlates with the physical status of HPV integration (66, 67).…”

Section: Natural History Of Mucosal Hpv Infectionsmentioning

confidence: 99%

Mucosal and Cutaneous Human Papillomavirus Infections and Cancer Biology

2019

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Papillomaviridae is a family of small non-enveloped icosahedral viruses with double-stranded circular DNA. More than 200 different human papillomaviruses (HPVs) have been listed so far. Based on epidemiological data, a subgroup of alphapapillomaviruses (alpha HPVs) was referred to as high-risk (HR) HPV types. HR HPVs are the etiological agents of anogenital cancer and a subset of head and neck cancers. The cutaneous HPV types, mainly from beta and gamma genera, are widely present on the surface of the skin in the general population. However, there is growing evidence of an etiological role of betapapillomaviruses (beta HPVs) in non-melanoma skin cancer (NMSC), together with ultraviolet (UV) radiation. Studies performed on mucosal HR HPV types, such as 16 and 18, showed that both oncoproteins E6 and E7 play a key role in cervical cancer by altering pathways involved in the host immune response to establish a persistent infection and by promoting cellular transformation. Continuous expression of E6 and E7 of mucosal HR HPV types is essential to initiate and to maintain the cellular transformation process, whereas expression of E6 and E7 of cutaneous HPV types is not required for the maintenance of the skin cancer phenotype. Beta HPV types appear to play a role in the initiation of skin carcinogenesis, by exacerbating the accumulation of UV radiation-induced DNA breaks and somatic mutations (the hit-and-run mechanism), and they would therefore act as facilitators rather than direct actors in NMSC. In this review, the natural history of HPV infection and the transforming properties of various HPV genera will be described, with a particular focus on describing the state of knowledge about the role of cutaneous HPV types in NMSC.

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Section: Natural History Of Mucosal Hpv Infectionsmentioning

confidence: 99%

Mucosal and Cutaneous Human Papillomavirus Infections and Cancer Biology

2019

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“…These results suggest that ISH has good concordance with qPCR with regards to the detection of HPV integration. Therefore, this method can be used for determining the physical status of HPV (41). The present study identified that women with LSIL (60%), with HSIL (65%) and with SCC (10%) had principally a mixed state.…”

Section: Discussionmentioning

confidence: 69%

“…It is important to note that in LSIL the number of altered cells is lower compared with HSIL. In addition, it has been reported that viral integration in SIL and CC is more frequently related to HPV16, 18 and 58 genotypes (41,46).…”

Section: Discussionmentioning

confidence: 99%

An increase of microRNA‑16‑1 is associated with the high proliferation of squamous intraepithelial lesions in the presence of the integrated state of HR‑HPV in liquid cytology samples

et al. 2020

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Studies of cervical cancer (CC) have reported that microRNA-16-1 (miR-16-1), which is an oncomiR, is increased in the tissues and cell lines of CC. The aim of the present study was to investigate the association of miRNA-16-1 expression level with squamous cell carcinoma (SCC), the presence of squamous intraepithelial lesions (SIL) and the integration of high-risk human papillomavirus (HR-HPV) DNA. The current study analyzed 80 samples obtained from women by liquid-based cytology, which revealed that 20 were negative for SIL (NSIL) and without HPV, 20 were low-grade SIL (LSIL), 20 were high-grade SIL (HSIL), and 20 were diagnosed as SCC with HR-HPV. The genotyping of the viral DNA was conducted via an INNO-LiPA-HPV array, the expression of miR-16-1 was determined by reverse transcription-quantitative PCR, and the physical state of the HR-HPV was ascertained by in situ hybridization with amplification with tyramide. A total of eight HR-HPV genotypes were distinguished; the most frequent of these being HPV16, followed by multiple infection with HR-HPV (including HPV16). The mixed state of the HR-HPV was observed in 60 and 65% of LSIL and HSIL cases, respectively, while an integrated HR-HPV state was identified in 90% of cases with SCC. The expression level of miR-16-1 increased according to the grade of SIL, and cases with HSIL exhibited a significantly higher miR-16-1 expression level compared with women with NSIL (P<0.001; Table II). It can therefore be determined that the expression of miR-16-1 effects cellular proliferation, due to the viral integration of various HR-HPV genotypes in unique infection or in multiple infection. Thus, the overexpression of miR-16-1 could be monitored in women with LSIL, in order to discard a major lesion.

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“…The L1 region of HPV is susceptible to DNA methylation which, interestingly, has been associated with lesion grade and viral integration. For example, methylation of CpG 5698 and 5617 is associated with high-grade lesions and CC ( Turan et al, 2006 ; Buck et al, 2013 ; Wang and Roden 2013 ; Torres-Rojas et al, 2018 ).…”

Section: Structure and Function Of Human Papillomavirus Genomementioning

confidence: 99%

Epigenetic and Transcriptomic Regulation Landscape in HPV+ Cancers: Biological and Clinical Implications

Castro-Oropeza

Piña‐Sánchez²

2022

Front. Genet.

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Human Papillomavirus (HPV) is an oncogenic virus that causes the highest number of viral-associated cancer cases and deaths worldwide, with more than 690,000 new cases per year and 342,000 deaths only for cervical cancer (CC). Although the incidence and mortality rates for CC are declining in countries where screening and vaccination programs have been implemented, other types of cancer in which HPV is involved, such as oropharyngeal cancer, are increasing, particularly in men. Mutational and transcriptional profiles of various HPV-associated neoplasms have been described, and accumulated evidence has shown the oncogenic capacity of E6, E7, and E5 genes of high-risk HPV. Interestingly, transcriptomic analysis has revealed that although a vast majority of the human genome is transcribed into RNAs, only 2% of transcripts are translated into proteins. The remaining transcripts lacking protein-coding potential are called non-coding RNAs. In addition to the transfer and ribosomal RNAs, there are regulatory non-coding RNAs classified according to size and structure in long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and small RNAs; such as microRNAs (miRNAs), piwi-associated RNAs (piRNAs), small nucleolar RNAs (snoRNAs) and endogenous short-interfering RNAs. Recent evidence has shown that lncRNAs, miRNAs, and circRNAs are aberrantly expressed under pathological conditions such as cancer. In addition, those transcripts are dysregulated in HPV-related neoplasms, and their expression correlates with tumor progression, metastasis, poor prognosis, and recurrence. Nuclear lncRNAs are epigenetic regulators involved in controlling gene expression at the transcriptional level through chromatin modification and remodeling. Moreover, disruption of the expression profiles of those lncRNAs affects multiple biological processes such as cell proliferation, apoptosis, and migration. This review highlights the epigenetic alterations induced by HPV, from infection to neoplastic transformation. We condense the epigenetic role of non-coding RNA alterations and their potential as biomarkers in transformation’s early stages and clinical applications. We also summarize the molecular mechanisms of action of nuclear lncRNAs to understand better their role in the epigenetic control of gene expression and how they can drive the malignant phenotype of HPV-related neoplasia. Finally, we review several chemical and epigenetic therapy options to prevent and treat HPV-associated neoplasms.

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Methylation of the L1 gene and integration of human papillomavirus 16 and 18 in cervical carcinoma and premalignant lesions

Cited by 12 publications

References 59 publications

Mucosal and Cutaneous Human Papillomavirus Infections and Cancer Biology

Mucosal and Cutaneous Human Papillomavirus Infections and Cancer Biology

An increase of microRNA‑16‑1 is associated with the high proliferation of squamous intraepithelial lesions in the presence of the integrated state of HR‑HPV in liquid cytology samples

Epigenetic and Transcriptomic Regulation Landscape in HPV+ Cancers: Biological and Clinical Implications

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