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The expression of Oct3/4A mRNA and not its isoforms is upregulated by the HPV16 E7 oncoprotein

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Abstract

Purpose

Oct3/4 a transcription factor is involved in maintaining the characteristics of cancer stem cells. Oct3/4 can be expressed differentially with respect to the progression of cervical cancer (CC). In addition, Oct3/4 can give rise to three isoforms by alternative splicing of the mRNA Oct3/4A, Oct3/4B and Oct3/4B1. The aim of this study was to evaluate the mRNA expression from Oct3/4A, Oct3/4B and Oct3/4B1 in low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), CC samples, and measure the effect of the HPV16 E7 oncoprotein on the mRNA expression from Oct3/4 isoforms in the C-33A cell line.

Methods

The expression levels of Oct3/4A, Oct3/4B and Oct3/4B1 mRNA were analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in patients with LSILs, HSILs and CC. Additionally, C-33A cells that expressed the HPV16 E7 oncoprotein were established to evaluate the effect of E7 on the expression of Oct3/4 mRNA isoforms.

Results

Oct3/4A (p = 0.02), Oct3/4B (p = 0. 001) and Oct3/4B1 (p < 0. 0001) expression is significantly higher in patients with LSIL, HSIL and CC than in woman with non-IL. In the C-33A cell line, the expression of Oct3/4A mRNA in the presence of the E7 oncoprotein increased compared to that in nontransfected C-33A cells.

Conclusion

Oct3/4B and Oct3/4B1 mRNA were expressed at similar levels among the different groups. These data indicate that only the mRNA of Oct3/4A is upregulated by the HPV16 E7 oncoprotein.

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Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

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Acknowledgements

We thank all of the Instituto Estatal de Cancerología ‘‘Dr. Arturo Beltrán Ortega’’ and Secretaría de Salud personnel who helped with this study at the clinic sites. We also thank technicians of Laboratorio de Biomedicina Molecular for their excellent laboratory assistance.

Funding

The present study was supported by grant from CONACYT, México (Investigación Científica Básica 2016; grant no. 288612).

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Author notes

  1. The authors Yazmín Gómez-Gómez and Jorge Organista-Nava contributed equally to this work.

Authors and Affiliations

  1. Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Edificio C primer piso, Av. Lázaro Cárdenas S/N, Ciudad Universitaria sur, 39090, Chilpancingo, Guerrero, México

    Yazmín Gómez-Gómez, Jorge Organista-Nava, Sayuri Itzel Clemente-Periván, Daniel Villanueva-Morales, Dania Yahaira Ayala-Reyna, Julio Ortiz-Ortiz, Ciresthel Bello-Rios, Marco Antonio Leyva-Vázquez & Berenice Illades‑Aguiar

  2. Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, 62100, Cuernavaca, Morelos, México

    Alfredo Lagunas-Martínez

  3. Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, 07360, Ciudad de México, Mexico

    Eric Genaro Salmerón-Bárcenas

  4. Laboratorio de Citopatología, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, 39090, Chilpancingo, Guerrero, México

    Luz del Carmen Alarcón-Romero

  5. Instituto Estatal de Cancerología “Dr. Arturo Beltrán Ortega”, 39570, Acapulco, Guerrero, México

    Marco Antonio Jiménez-López

Authors
  1. Yazmín Gómez-Gómez
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  2. Jorge Organista-Nava
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Contributions

Gómez-Gómez Y: Data collection, Validation, Formal analysis, and Manuscript original draft preparation. Organista-Nava J: Conceptualization, Data collection, Validation, Formal analysis, Project administration, Manuscript writing—review and editing. Clemente-Periván SI: Data collection, Formal analysis, and Manuscript original draft preparation. Lagunas-Martínez A: Data collection. Salmerón-Bárcenas EG: Data collection, and Formal analysis. Villanueva-Morales D: Data collection. Ayala-Reyna DY: Data collection. Alarcón-Romero L del C: Data collection. Ortiz-Ortiz J: Data collection. Bello-Rios C: Data collection. Jiménez-López MA: Data collection. Leyva-Vázquez MA: Data collection. Illades-Aguiar B: Conceptualization, Project administration and Funding acquisition. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Jorge Organista-Nava or Berenice Illades‑Aguiar.

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The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Bioethical Committee of the Universidad Autónoma de Guerrero and Instituto Estatal de Cancerología ‘‘Dr. Arturo Beltrán Ortega’’ (approval no. FO-INV-AUT2018).

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This study was conducted in accordance with the guidelines of the Declaration of Helsinki. Written informed consent was obtained from all participants prior your registration in this study. Data confidentiality was maintained throughout the study.

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Gómez-Gómez, Y., Organista-Nava, J., Clemente-Periván, S.I. et al. The expression of Oct3/4A mRNA and not its isoforms is upregulated by the HPV16 E7 oncoprotein. Mol Biol Rep 50, 981–991 (2023). https://doi.org/10.1007/s11033-022-07988-9

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