Vitamin A deficiency in K14E7HPV expressing transgenic mice facilitates the formation of malignant cervical lesions

Ocadiz-Delgado, Rodolfo; Serafín-Higuera, Nicolás; Álvarez-Ríos, Elizabeth; García‐Villa, Enrique; Tinajero-Rodríguez, Manuel; Rodríguez-Uribe, Genaro; Escobar-Wilches, Derly Constanza; Albino‑Sanchez, M. E.; Ramírez-Rosas, Alejandro; Sierra-Santoyo, Adolfo; Hernández-Pando, Rogelio; Lambert, Paul F.; Gariglio, Patricio

doi:10.1111/apm.13159

Cited by 5 publications

(5 citation statements)

References 33 publications

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“…In fact, retinoids have the ability to inhibit cell proliferation through the tumor suppressor RARβ. [17][18][19][20] According to our observations, a single E 2 stimulus was enough to decrease the levels of apoptosis in both the FvB and K14E7 mice. Previous studies have demonstrated that E 2 has the ability to inhibit apoptosis mediated by estrogen receptors.…”

Section: Discussionmentioning

confidence: 52%

“…Among the possible metabolites responsible for the antiproliferative activity of ELj, is retinol, whose intake has been proposed to reduce the risk of CC since it has been shown that this molecule is capable of regulating multiple cellular processes since the cervical epithelium is highly sensitive to Vitamin A. In fact, retinoids have the ability to inhibit cell proliferation through the tumor suppressor RARβ 17‐20 …”

Section: Discussionmentioning

confidence: 99%

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Laurencia johnstonii extract reverses early lesions in the K14E7HPV16 murine cervical carcinogenesis model

Arvizu‐Hernandez,

Hernandez‐Guerrero,

Alvarez‐Rios

et al. 2024

Journal of Medical Virology

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Persistent infection with high‐risk human papillomavirus (HR‐HPV) is a well‐established risk factor to the development of cervical intraepithelial neoplasia (CIN), a condition that can progress to cervical cancer (CC) a major health problem worldwide. Recently, there has been growing interest in exploring alternative therapies utilizing natural products, among which is the algae species Laurencia johnstonii Setchell & Gardner, 1924 (L. johnstonii), proposed for the management of precancerous lesions. The aim of this work was to determine the effect of an organic extract from L. johnstonii (ELj) in early cervical lesions (CIN 1). These CIN 1 lesions were generated in a murine model expressing the HR‐HPV16 E7 oncoprotein (K14E7HPV transgenic mice) with a single exogenous hormonal stimulus using 17β‐estradiol. The histopathological studies, the determination of cell proliferation and of the apoptotic levels in cervical tissue, showed that, seven doses of ELj (30 mg/kg weight per day diluted in a DMSO‐saline solution [1:7]) lead to recovery the architecture of cervical epithelium. Accordingly, in the transgenic mice it was observed a statistically significant decrease of the PCNA expression levels, a marker of cell proliferation, and a statistically significant increase in the apoptosis levels using Caspase 3 as a marker. In addition, we determined the expression levels of the tumor suppressor miR‐218 and the oncomiRNA miR‐21. Interestingly, our results may suggest that ELj treatment tended to restore the normal expression of both miRNAs as compared with controls being more evident in the non‐transgenic induced mice. Differences of p < 0.05 were considered statistically significant through the whole study. Based on these results, we propose that the use of ELj could be an alternative for the treatment of cervical early lesions.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Laurencia johnstonii extract reverses early lesions in the K14E7HPV16 murine cervical carcinogenesis model

Arvizu‐Hernandez,

Hernandez‐Guerrero,

Alvarez‐Rios

et al. 2024

Journal of Medical Virology

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“…Interestingly, researchers also found that the chronic stress and diurnal cortisol also play an important role in HR‐HPV infection and HPV‐associated cervical carcinogenesis 295 . Furthermore, dietary factors also appear to play an important role in the animal experiment and human clinical research and both show that diets with low antioxidants (vitamin A, B2, E, and folate) are more likely to develop HPV infections 296,297 …”

Section: Hpv and Its Pathogenesismentioning

confidence: 99%

“… 295 Furthermore, dietary factors also appear to play an important role in the animal experiment and human clinical research and both show that diets with low antioxidants (vitamin A, B2, E, and folate) are more likely to develop HPV infections. 296 , 297 …”

Section: Hpv and Its Pathogenesismentioning

confidence: 99%

Human papillomavirus associated cervical lesion: pathogenesis and therapeutic interventions

Ye,

Zheng,

et al. 2023

MedComm

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Human papillomavirus (HPV) is the most prevalent sexually transmitted virus globally. Persistent high‐risk HPV infection can result in cervical precancerous lesions and cervical cancer, with 70% of cervical cancer cases associated with high‐risk types HPV16 and 18. HPV infection imposes a significant financial and psychological burden. Therefore, studying methods to eradicate HPV infection and halt the progression of precancerous lesions remains crucial. This review comprehensively explores the mechanisms underlying HPV‐related cervical lesions, including the viral life cycle, immune factors, epithelial cell malignant transformation, and host and environmental contributing factors. Additionally, we provide a comprehensive overview of treatment methods for HPV‐related cervical precancerous lesions and cervical cancer. Our focus is on immunotherapy, encompassing HPV therapeutic vaccines, immune checkpoint inhibitors, and advanced adoptive T cell therapy. Furthermore, we summarize the commonly employed drugs and other nonsurgical treatments currently utilized in clinical practice for managing HPV infection and associated cervical lesions. Gene editing technology is currently undergoing clinical research and, although not yet employed officially in clinical treatment of cervical lesions, numerous preclinical studies have substantiated its efficacy. Therefore, it holds promise as a precise treatment strategy for HPV‐related cervical lesions.

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“…Another therapeutic resource for HPV neoplasms is the systemic administration of retinoids such as vitamin A ( Oren-Shabtai et al, 2021 ), due to the retinoid deficiency is associated with the methylation of the retinoic acid receptor β 2 (RARβ2), a tumor suppressor. In a transgenic mouse model, it was shown that the expression of HPV E7 and the lack of dietary retinoids induce proliferation, hyperkeratinization, development of precursor lesions, and cancer in situ ( Ocadiz-Delgado et al, 2021 ).…”

Section: Epigenetic Therapy and Chemopreventionmentioning

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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Vitamin A deficiency in K14E7HPV expressing transgenic mice facilitates the formation of malignant cervical lesions

Cited by 5 publications

References 33 publications

Laurencia johnstonii extract reverses early lesions in the K14E7HPV16 murine cervical carcinogenesis model

Laurencia johnstonii extract reverses early lesions in the K14E7HPV16 murine cervical carcinogenesis model

Human papillomavirus associated cervical lesion: pathogenesis and therapeutic interventions

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

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