Gloria Fernández-Tilapa

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.

miR-23b-3p, miR-124-3p and miR-218-5p Synergistic or Additive Effects on Cellular Processes That Modulate Cervical Cancer Progression? A Molecular Balance That Needs Attention

In cervical cancer (CC), miR-23b-3p, miR-124-3p, and miR-218-5p have been found to act as tumor suppressors by regulating cellular processes related to progression and metastasis. The objective of the present review is to provide an update on the experimental evidence about the role of miR-23b-3p, miR-124-3p, and miR-218-5p in the regulation of CC progression. Additionally, we present the results of a bioinformatic analysis that suggest that these miRNAs have a somewhat redundant role in the same cellular processes that may result in a synergistic effect to promote CC progression. The results indicate that specific and common target genes for miR-23b-3p, miR-124-3p, and miR-218-5p regulate proliferation, migration, apoptosis, and angiogenesis, all processes that are related to CC maintenance and progression. Furthermore, several target genes may regulate cancer-related signaling pathways. We found that a total of 271 proteins encoded by the target mRNAs of miR-23b-3p, miR-124-3p, or miR-218-5p interact to regulate the cellular processes previously mentioned, and some of these proteins are regulated by HPV-16 E7. Taken together, information analysis indicates that miR-23b-3p, miR-124-3p, and miR-218-5p may potentiate their effects to modulate the cellular processes related to the progression and maintenance of CC with and without HPV-16 involvement.

Overexpression of miR-23b–3p+miR-218-5p+miR-124-3p differentially modifies the transcriptome of C-33A and CaSki cells and the regulation of cellular processes involved in the progression of cervical cancer

Dysregulation of tumor suppressor miRNAs (tsmiRs) is associated with tumor progression in cancer. miR-23b-3p, miR-218-5p and miR-124-3p are tsmiRs in cervical cancer (CC) and regulate the translation of genes involved in metastasis-related biological processes. To analyze transcriptome changes in cervical cancer cell lines (C-33A HPV-negative and CaSki HPV-positive) overexpressing miR-23b-3p + miR-218-5p + miR-124-3p, to identify specific target transcripts common to all three miRNAs, as well as signaling pathways and cellular processes related to tumor progression. The transcriptome of C-33A and CaSki cells transfected with miR-23b-3p + miR-218-5p + miR-124-3p was analyzed by RNA-seq. Differentially expressed genes (DEGs) were subjected to Gene Ontology analysis on the DAVID platform. The function of under-regulated genes was analyzed on the GEPIA 2.0, Kaplan-Meier plotter and STRING platforms. On the TargetScanHuman platform it was determined which transcripts have MREs for miR-23b-3p, miR-218-5p and/or miR-124-3p in their 3'UTR region. Simultaneous overexpression of miR-218-5p, miR-124-3p and miR-23b-3p induced changes in global gene expression in C-33A and CaSki cells. In C-33A cells, DEGs included 45 over- and 172 under-regulated transcripts; in CaSki, 125 transcripts were over- and 84 under-regulated. The under-regulated transcripts enrich proliferation, migration, apoptosis and angiogenesis; 20 of these genes are associated with overall survival (OS) in women with CC, and 18 of the 20 mRNAs have MREs for one, two or all three miRNAs. miR-23b-3p + miR-218-5p + miR-124-3p, differentially modify global gene expression in C-33A and CaSki cells. The results indicate that these miRNAs act synergistically and modulate CC progression through individual and shared targets by two or all three miRNAs.