Investigator
Instituto Politcnico Nacional
Exometabolome and Molecular Signatures Associated with HPV 16 in Cervical Cancer: Integrative Metabolomic and Transcriptomic Analysis for Biomarker Discovery
Cervical cancer (CC) represents a major public health concern, ranking as the fourth most frequently diagnosed cancer and one of the leading causes of cancer-related mortality among middle-aged women worldwide. CC is caused by persistent infection with high-risk human papillomaviruses (HR-HPVs), with HPV 16 being the cause of more than 50% of CC cases. In this study, the exometabolome of the HPV 16-positive cell lines SiHa and Ca Ski, as well as the HPV 16-negative control cell line C-33 A, was evaluated. The exometabolome was validated through molecular signatures using a transcriptomic approach to identify genes encoding cellular metabolic enzymes. The exometabolome was analyzed using 1H nuclear magnetic resonance spectroscopy (1H-NMR). Exometabolomic profiles were subsequently compared through both multivariate and univariate statistical analyses to identify significant differences between cell lines. Molecular signatures were analyzed from the GSE9750 dataset obtained from the GEO database. Exometabolic profiling of the HPV 16 positive cell lines showed higher concentrations of leucine, isoleucine, valine, lysine, methionine, glutamine, ornithine, choline, glucose, and tryptophan. An expression analysis showed increased expression of enzymes involved in amino acid synthesis, the tricarboxylic acid cycle, glycolysis, the pentose phosphate pathway, galactose metabolism, and HIF-1α. These data suggest metabolites and metabolism-associated genes that can be used as non-invasive, stable diagnostic and prognostic biomarkers, as well as therapeutic targets for CC in the presence of HPV 16.
Mortality burden of malignant neoplasms of the corpus uteri in Mexico: an analysis of trends from 2000 to 2022
ABSTRACT Objective: The aim of this study was to analyze temporal trends in malignant neoplasms of corpus uteri mortality in México from 2000 through 2022. Methods: Certificates of death were analyzed. The age-standardized mortality rate (ASMR), the number of years of life lost, according to the federal state, was estimated. The changes in temporal trends were analyzed using joint point regression. Results: The ASMR from malignant neoplasms of the corpus uteri was estimated at 2.5 (95% confidence interval [CI] 2.2–2.8), and the annual percentage change from 2000 to 2018 was 4.32. The age group of 60–65 years was most affected. Conclusion: This report indicates an increase in the ASMR from malignant neoplasms of the corpus uteri. It also suggests the need for the development of public health laws focusing on the early diagnosis and prevention of uterine cancer.
MiR-21 Regulates Growth and Migration of Cervical Cancer Cells by RECK Signaling Pathway
Expression of miR-21 has been found to be altered in almost all types of cancers, and it has been classified as an oncogenic microRNA. In addition, the expression of tumor suppressor gene RECK is associated with miR-21 overexpression in high-grade cervical lesions. In the present study, we analyze the role of miR-21 in RECK gene regulation in cervical cancer cells. To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression using siRNAs. We analyzed the expression of miR-21 and RECK, as well as functional effects on cell proliferation and migration. We found that in cervical cancer cells, there was an inverse correlation between miR-21 expression and RECK mRNA and protein expression. SiRNAs to miR-21 increased luciferase reporter activity in construct plasmids containing the RECK-3′-UTR microRNA response elements MRE21-1, MRE21-2, and MRE21-3. The role of miR-21 in cell proliferation was also analyzed, and cancer cells transfected with siRNAs exhibited a markedly reduced cell proliferation and migration. Our findings indicate that miR-21 post-transcriptionally down-regulates the expression of RECK to promote cell proliferation and cell migration inhibition in cervical cancer cell survival. Therefore, miR-21 and RECK may be potential therapeutic targets in gene therapy for cervical cancer.
