Hiram Hernández-López

Differentially Expressed Genes Associated with the Development of Cervical Cancer

Cervical cancer remains a significant cause of cancer-related mortality among women, particularly in low- and middle-income countries. High-throughput technologies, such as microarrays, have facilitated the comprehensive analysis of gene expression profiles in cervical cancer, enabling the identification of key differentially expressed genes (DEGs) involved in its pathogenesis. The publicly available microarray datasets, including GSE39001, GSE9750, GSE7803, GSE6791, GSE63514, and GSE52903 in combination with bioinformatics database predictions, were used to identify differential expression genes, potential biomarkers, and therapeutic targets for cervical cancer; additionally, we undertook bioinformatic analysis to determine gene ontology and possible miRNA targets related to our DEGs. Our analysis revealed several DEGs significantly associated with cervical cancer progression, such as cell death, regulation of DNA replication, protein binding processes, and transcription factors. The most relevant transcription factors (TFs) identified were SP1, ELF3, E2F1, TP53, RELA, HDAC, and FOXM1. Importantly, the DEGs with more important changes were 11 coding genes that were upregulated (KIF4A, MCM5, RFC4, PLOD2, MMP12, PRC1, TOP2A, MCM2, RAD51AP1, KIF20A, AIM2) and 14 that were downregulated (CXCL14, KRT1, KRT13, MAL, SPINK5, EMP1, CRISP3, ALOX12, CRNN, SPRR3, PPP1R3C, IVL, CFD, CRCT1), which were associated with cervical cancer. Interestingly, hub proteins KIF4A, NUSAP1, BUB1B, CEP55, DLGAP5, NCAPG, CDK1, MELK, KIF11, and KIF20A were found to be potentially regulated by several miRNAs, including miR-107, miR-124-3p, miR-147a, miR-16-5p, miR-34a-5p, miR-34c-5p, miR-126-3p, miR-10b-5p, miR-23b-3p, miR-200b-3p, miR-138-5p, miR-203a-3p, miR-214-3p, and let-7b-5p. The relationship between these genes highlights their potential as candidate biomarkers for further research in treatment, diagnosis, and prognosis.

Differential Proliferation Effect of the Newly Synthesized Valine, Tyrosine and Tryptophan–Naphthoquinones in Immortal and Tumorigenic Cervical Cell Lines

We previously showed that microwave assisted synthesis is the best method for the synthesis of naphthoquinone amino acid and chloride-naphthoquinone amino acid derivatives by a complete evaluation of reaction conditions such as stoichiometry, bases, and pH influence. Following the same strategy, we synthesized chloride and non-chloride tyrosine, valine, and tryptophan-naphthoquinones achieving 85–95%, 80–92%, and 91–95% yields, respectively. The cyclic voltammetry profiles showed that both series of naphthoquinone amino acid derivatives mainly display one redox reaction process. Overall, chloride naphthoquinone amino acid derivatives exhibited redox potential values (E1/2) more positive than non-chloride compounds. The six newly synthesized compounds were tested in HPV positive and negative as well as in immortal and tumorigenic cell lines to observe the effects in different cellular context simulating precancerous and cancerous status. A dose-response was achieved to determine the IC50 of six newly synthesized compounds in SiHa (Tumorigenic and HPV16 positive), CaLo (Tumorigenic and HPV18 positive), C33-A (Tumorigenic and HPV negative) and HaCaT (Keratinocytes immortal HPV negative) cell lines. Non-chloride tryptophan-naphthoquinone (3c) and chloride tyrosine-naphthoquine (4a) effects were more potent in tumorigenic SiHa, CaLo, and C33-A cells with respect to non-tumorigenic HaCaT cells. Interestingly, there seems to be a differential effect in non-chloride and chloride naphthoquinone amino acid derivatives in tumorigenic versus non tumorigenic cells. Considering all naphthoquinone amino acid derivatives that our group synthesized, it seems that hydrophobic and aromatic amino acids have the greatest effect on cell proliferation inhibition. These results show promising compounds for cervical cancer treatment.