Abstract
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.
Highlights
Cervical cancer is the fourth most common cancer in women worldwide, with an estimated global incidence of 570,000 new cases and over 311,000 deaths per year [1]
We searched for binding sites of micro RNA (miR)-34 family members in MMP2 and/or matrix metalloproteinase 9 (MMP9) messenger RNA (mRNA), and we found that miR-34a-5p and miR-34c-5p had binding sites for these genes (Figure 2C)
We found that miR-34a-5p has a remarkable effect in cell migration and invasion that, in part, could be explained by MMP9 activity inhibition and downregulation of microtubule-associated protein 2 (MAP2) in SiHa cells; MMP2 was not affected by this miRNA
Summary
Cervical cancer is the fourth most common cancer in women worldwide, with an estimated global incidence of 570,000 new cases and over 311,000 deaths per year [1]. High-risk human papillomavirus (HPV) infection is associated with the development of cervical, penile, and anal cancers. High-risk HPV expression appears necessary to immortalize and stimulate proliferation in human keratinocytes [2], it is not sufficient to produce a fully transformed phenotype, suggesting that other genetic changes participate in the development of cervical cancer [3]. MicroRNAs (miRNAs) are small non-coding RNAs 21–25 nucleotides (nt) in length grouped in families with similar, as well as specific and unique, targets associated with cellular processes and molecular targets that remain largely undefined and experimentally untested [4,5]. The members of different miRNA families present overlapping messenger RNA (mRNA) targets and tissue specificity [7]. Single-strand mature miRNAs have the coding potential to hybridize with very different complementary mRNA targets
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
