Genes Involved in the Transcriptional Regulation of Pluripotency Are Expressed in Malignant Tumors of the Uterine Cervix and Can Induce Tumorigenic Capacity in a Nontumorigenic Cell Line

Abstract

Transcription factors OCT4, SOX2, KLF4, C-MYC, and NANOG (OSKM-N) regulate pluripotency and stemness, and their ectopic expression reprograms human and murine fibroblasts that constitute the key of regenerative medicine. To determine their contribution to cell transformation, we analyzed the gene expression profiles of these transcription factors in cervical cancer samples and found that they are preferentially expressed in the tumor component. Also, cancer stem cell-enriched cultures grown as sphere cultures showed overexpression of OSKM-N genes. Importantly, we observed that lentiviral-mediated transduction of these factors confers, to a nontumorigenic immortalized human cell line, properties of cancer stem cells as the ability to form tumors in a mouse model. When we performed a meta-analysis using microarray data from cervical cancer biopsies and normal tissues, we found that the expression of OSKM-N and some target genes allowed separating tumor and normal tissues between samples, which enhanced the importance of OSKM-N in the tumorigenesis. Finally, we analyzed and compared both transcript and protein expression profiles of these factors within a cohort of patients with cervical cancer. To our knowledge, this is the first time that the expression of OSKM-N is described to induce one of the main characteristics of the cancer stem cell, the tumorigenicity. And, more importantly, its exogenous expression in a nontumorigenic cell line is sufficient to induce a tumorigenic phenotype; furthermore, the differential expression of this transcription factor distinguishes tumor tissue and normal tissue in cervical samples.

SOX2 and Bcl-2 as a Novel Prognostic Value in Hepatocellular Carcinoma Progression

“…We found SOX2 mRNA expression in HCC tissue samples more than two folds higher than the normal tissue samples. Our results were consistent with studies showing SOX2 overexpression in gastric cancer [22], lung squamous cell carcinoma [23], gastrointestinal cancers [12], cervical cancer [24], gliomas [25], and pancreatic carcinoma [3,26].…”

Nanog, in Cooperation with AP1, Increases the Expression of E6/E7 Oncogenes from HPV Types 16/18

“…Expression of E7/E6 has been shown to be regulated by several transcription factors associated with cancer, pluripotency, and regulation of stem cells. Nanog has been shown to be expressed in malignant tumors of the uterine cervix, and high expression associated with poor tumor prognosis [ 46 , 47 ].…”

The occurrence and development of induced pluripotent stem cells

“…Retroviruses can only be applied to dividing cells, which greatly limits their clinical application ( Miller et al, 1990 ). The delivery of reprogramming factors through lentiviral vectors is another successful method that has greater reprogramming efficiency and less variability than the use of retroviruses ( Jung et al, 2014 ; Gurusinghe et al, 2015 ; Chen et al, 2016 ; Abbey et al, 2019 ; Pessôa et al, 2019a ; Gurusinghe et al, 2019 ; Khoshchehreh et al, 2019 ; Ruiz et al, 2019 ; Hernández-Sapiéns et al, 2020 ; Jiang et al, 2020 ; Chandrasekaran et al, 2021 ; Güney-Esken et al, 2021 ). Lentiviruses can transduce nondividing cells and exhibit selective tropism, which is conducive to high-level continuous expression of factors ( Yu et al, 2007 ).…”