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Molecular changes in adipocyte-derived stem cells during their interplay with cervical cancer cells



Obesity is as an important risk factor and has been associated with a worse prognosis in at least 13 distinct tumor types. This is partially due to intercellular communication between tumor cells and adipose tissue-derived stem cells (ADSCs), which are increased in obese individuals. As yet, however, little is known about the molecular changes occurring in ADSCs in these conditions. Cervical cancer has a high incidence and mortality rate in women from developing countries, particularly in those with a high body mass index (BMI).


We analyzed the expression profile of ADSCs co-cultured with cervical cancer cells through massive RNA sequencing followed by evaluation of various functional alterations resulting from the modified transcriptome.


A total of 761 coding and non-coding dysregulated RNAs were identified in ADSCs after co-culture with HeLa cells (validation in CaSki and SiHA cells). Subsequent network analysis showed that these changes were correlated with migration, stemness, DNA repair and cytokine production. Functional experiments revealed a larger ALDHhigh subpopulation and a higher migrative capacity of ADSCs after co-culture with HeLa cells. Interestingly, CXCL3 and its intragenic long-noncoding RNA, lnc-CXCL3, were found to be co-regulated during co-culture. A loss-of-function assay revealed that lnc-CXCL3 acts as a key regulator of CXCL3 expression.


Our results suggest that intercellular communication between ADSCs and cervical cancer cells modifies the RNA expression profile in the former, including that of lncRNAs, which in turn can regulate the expression of diverse chemokines that favor malignancy-associated capacities such as migration.

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Data availability

The data obtained from the sequencing were deposited: SRA data: PRJNA780960.


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This work was part of the PhD thesis of Marcela Angelica De la Fuente Hernandez (CVU: 441075) from the Programa de Doctorado en Ciencias Biológicas, Universidad Nacional Autónoma de México (UNAM). The work was supported by a Consejo Nacional de Ciencia y Tecnologia (CONACyT) fellowship (Registry number 270150). We thank Dr. Alfredo Mendoza for his help in transcriptome sequencing (Unit of Sequencing Genomics, Instituto Nacional de Medicina Genomica, Mexico City), M.C. Linda Nelly Patiño for her help in the cytometry experiments (Unit of Citometry, Instituto Nacional de Medicina Genómica, Mexico City), M.C. Miguel Angel Sarabia Sanchez for his help in the cytometry experiments in the Laboratorio Nacional de Citometría de Flujo (LabNalCit), Mexico City and Dr. Daniel Díaz for his kind assistance in proofreading this manuscript.


Marcela Angelica De la Fuente Hernandez is a doctoral student from Programa de Doctorado en Ciencias Biologicas, Universidad Nacional Autonoma de México (UNAM) and received a fellowship 270150 from CONACyT. This work was supported by grant A1-S-33543 CONACyT to Vilma Maldonado.

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Authors and Affiliations



MDH: substantial contributions to the conception and design of the study; substantial contributions to data acquisition and analysis and drafting the article. EAM: established the primary culture. EFO: contributed to the selection and enrollment of patients for obtaining visceral adipose tissue. ARG: contributed to the selection and enrollment of patients for obtaining visceral adipose tissue. LAP: contributed to the revision of the manuscript. KVS: contributed to the GSEA analysis of the RNAseq data. JMZ: made substantial contributions to the analysis and interpretation of sequencing data. VFO: contributed to the revision of the manuscript. RMAG: Contributed to the revision of the manuscript. VML: made substantial contributions to the conception and design of the study, coordinated the work, analyzed the data and contributed to the manuscript draft.

Corresponding author

Correspondence to Vilma Maldonado Lagunas.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards and consent to participate.

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Not applicable. Inthe manuscript, no data is handled that puts the identity or privacy of the donor at risk.

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The authors declare that there is no conflict of interest.

Research involving human participants

Morbidly obese women undergoing gastric bypass donor visceral adipose tissue.

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Informed consent was obtained from all individual participants included in the study.

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De la Fuente-Hernandez, M.A., Alanis-Manriquez, E.C., Ferat-Osorio, E. et al. Molecular changes in adipocyte-derived stem cells during their interplay with cervical cancer cells. Cell Oncol. 45, 85–101 (2022).

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  • Cervical cancer
  • Obesity
  • ADSC
  • HeLa
  • Transcriptome
  • lncRNA
  • Intercellular communication