Aberrant miRNA expression is well recognized as an important step in the development of cancer. Close to 70 microRNAs (miRNAs) have been implicated in cervical cancer up to now, nevertheless it is unknown if aberrant miRNA expression causes the onset of cervical cancer. One of the best ways to address this issue is through a multistep model of carcinogenesis. In the progression of cervical cancer there are three well-established steps to reach cancer that we used in the model proposed here. The first step of the model comprises the gene changes that occur in normal cells to be transformed into immortal cells (CIN 1), the second comprises immortal cell changes to tumorigenic cells (CIN 2), the third step includes cell changes to increase tumorigenic capacity (CIN 3), and the final step covers tumorigenic changes to carcinogenic cells. Altered miRNAs and their target genes are located in each one of the four steps of the multistep model of carcinogenesis. miRNA expression has shown discrepancies in different works; therefore, in this model we include miRNAs recording similar results in at least two studies. The present model is a useful insight into studying potential prognostic, diagnostic, and therapeutic miRNAs.

Tumor cells have developed advantages to acquire hallmarks of cancer like apoptosis resistance, increased proliferation, migration, and invasion through cell signaling pathway misregulation. The sequential activation of genes in a pathway is regulated by miRNAs. Loss or gain of miRNA expression could activate or repress a particular cell axis. It is well known that aberrant miRNA expression is well recognized as an important step in the development of cancer. Individual miRNA expression is reported without considering that miRNAs are grouped in clusters and may have similar functions, such as the case of clusters with anti-oncomiRs (23b~27b~24-1, miR-29a~29b-1, miR-29b-2~29c, miR-99a~125b-2, miR-99b~125a, miR-100~125b-1, miR-199a-2~214, and miR-302s) or oncomiRs activity (miR-1-1~133a-2, miR-1-2~133a-1, miR-133b~206, miR-17~92, miR-106a~363, miR183~96~182, miR-181a-1~181b-1, and miR-181a-2~181b-2), which regulated mitogen-activated protein kinases (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), NOTCH, proteasome-culling rings, and apoptosis cell signaling. In this work we point out the pathways regulated by families of miRNAs grouped in 20 clusters involved in cervical cancer. Reviewing how miRNA families expressed in cluster-regulated cell path signaling will increase the knowledge of cervical cancer progression, providing important information for therapeutic, diagnostic, and prognostic methodology design.

The micro RNA (miR)-34 family is composed of 5p and 3p strands of miR-34a, miR-34b, and miR-34c. The 5p strand’s expression and function is studied in cervical cancer. The 3p strand’s function and regulation remain to be elucidated. To study the function of the passenger strands of miR-34 family members, we overexpressed 5p and 3p strands using a synthetic miRNA in cervical cell lines. Cell proliferation was evaluated using crystal violet. Migration and invasion were tested using transwell assays, Western blot, and zymography. Possible specific targets and cell signaling were investigated for each strand. We found that miR-34a-5p inhibited proliferation, migration, and cell invasion accompanied by matrix metalloproteinase 9 (MMP9) activity and microtubule-associated protein 2 (MAP2) protein reduction. We also found that miR-34b-5p and miR-34c-5p inhibit proliferation and migration, but not invasion. In contrast, miR-34c-5p inhibits MMP9 activity and MAP2 protein, while miR-34b-5p has no effect on these genes. Furthermore, miR-34a-3p and miR-34b-3p inhibit proliferation and migration, but not invasion, despite the later reducing MMP2 activity, while miR-34c-3p inhibit proliferation, migration, and cell invasion accompanied by MMP9 activity and MAP2 protein inhibition. The difference in cellular processes, MMP2 and MMP9 activity, and MAP2 protein inhibition by miR-34 family members suggests the participation of other regulated genes. This study provides insights into the roles of passenger strands (strand*) of the miR-34 family in cervical cancer.

Aberrant miRNA expression is well recognized as a cancer hallmark, nevertheless miRNA function and expression does not always correlate in patients tissues and cell lines studies. In addition to this issue, miRNA strand usage conduces to increased cell signaling pathways modulation diversifying cellular processes regulation. In cervical cancer, 20 miRNA families are involved in carcinogenesis induction and development to this moment. These families have 5p and 3p strands with different nucleotide (nt) chain sizes. In general, mature 5p strands are larger: two miRNAs of 24 nt, 24 miRNAs of 23 nt, 35 miRNAs of 22 nt and three miRNAs of 21 nt. On the other hand, the 3p strands lengths observed are: seven miRNAs of 23 nt, 50 miRNAs of 22 nt, six miRNAs of 21 nt and four miRNAs of 20 nt. Based on the analysis of the 20 miRNA families associated with cervical cancer, 67 3p strands and 65 5p strands are selected suggesting selectivity and specificity mechanisms regulating cell processes like proliferation, apoptosis, migration, invasion, metabolism and Warburg effect. The insight reviewed here could be used in the miRNA based therapy, diagnosis and prognosis approaches.

Quinolones are a family of antimicrobial agents that have been used in antibacterial and anticancer chemotherapy. Fluoroquinolone targets DNA gyrase and topoisomerase IV enzymes affecting several cellular processes, like cell death and proliferation; the best way to act is in the form of carboxylic acid or, recently, as quinolone-metal complex. In this work, the use of boron is shown as an alternative of metal to form a complex by incorporating to fluoroquinolone as an electron withdrawing substituent to activate the C-7 position chemoselectively for the production of new fluoroquinolone hybrids and test their effects on cell proliferation. Fluoroquinolone-boron complexes were synthesized according to the Gould-Jacobs cyclization method, and five hybrid fluoroquinolone-boron compounds were obtained by S N Ar reaction, yielding 31 to 46%, at 80°C, and in 10 to 25 hours of reaction. e effect of the five fluoroquinolone-boron hybrids was evaluated in cervical cancer cell lines by cell proliferation assay. 7-hydantoin-fluoroquinolone-boron and 7-dihydropyridine-fluoroquinolone-boron complexes showed the strongest effect according to dose-response assay, respectively. e fluoroquinolone-boron hybrid complex showed proliferation inhibition in SiHa and CasKi cells, opening the possibility to use them as potential agents for the treatment of cancer.