Abstract
BackgroundAround the world, cervical cancer is the fourth most common cancer among women. MicroRNAs (miRNAs) and agents that target mRNAs have been introduced as novel diagnostic markers and therapeutic approaches, respectively, in cancer. MiRNA-486-5p is a candidate regulator of phosphatase and tensin homolog (PTEN) in silico, and the downregulation of PTEN in cervical cancer is not consistent with its mutation, which suggests that PTEN may be subjected to post-transcription modification moderated by miRNAs. Here, we aimed to explore whether miR-486-5p is a regulator in the development of cervical cancer through the PI3K/Akt pathway by targeting PTEN.MethodsThe expression level of miR-486-5p in human cervical cancer serum and tissues were analyzed through quantitative RT-PCR. Human cervical cancer cell lines HeLa and SiHa were selected to explore the effects of miR-486-5p downregulated or overexpression on cell proliferation, migration, and invasion, respectively. Moreover, we observed the effect of miR-486-5p downregulated on tumorigenesis using HeLa cell in vivo. Besides, the relationship between miR-486-5p and PTEN were determined by dual luciferase reporter gene assay.ResultsCompared to control subjects, miR-486-5p was significantly overexpressed in cervical cancer patients’ serum and tissues. Suppression of miR-486-5p expression significantly inhibited HeLa cell proliferation, colony formation, migration, and invasion, as well as tumor growth in nude mice, while miR-486-5p overexpression stimulated SiHa cell proliferation, colony formation, migration, and invasion. We also confirmed that miR-486-5p directly targeted the 3′-untranslated region of the tumor-suppressor gene PTEN, inhibiting its expression, and that overexpression of miR-486-5p activated the PI3K/Akt pathway.ConclusionsWe conclude that miR-486-5p stimulates cell proliferation, migration, and invasion through inhibition of PTEN expression and activation of the oncogenic PI3K/Akt pathway in cervical cancer. Our findings implicate serum miR-486-5p as a novel molecular biomarker that may provide effective approaches to both diagnosis and treatment in cervical cancer.
Highlights
Around the world, cervical cancer is the fourth most common cancer among women
MiR-486-5p activates the Phosphatidyl Inositol 3-kinase (PI3K)-Protein kinase B (Akt) pathway by directly inhibiting phosphatase and tensin homolog (PTEN) To understand the mechanisms underlying the effects of miR-486-5p on cervical cancer, we examined the potential target of miR-486-5p by in silico analysis using the TargetScanHuman6.2 database
Some reports suggest that miR486-5p is a tumor suppressor in lung cancer [14] and gastric adenocarcinoma [13], while others indicate that it is oncogenic in myeloid leukemia of Down syndrome [11] and chronic myeloid leukemia [12]
Summary
Cervical cancer is the fourth most common cancer among women. MicroRNAs (miRNAs) and agents that target mRNAs have been introduced as novel diagnostic markers and therapeutic approaches, respectively, in cancer. Cervical cancer is the fourth most common cancer among women, accounting for an estimated 529,572 diagnosed new cases and 274,967 deaths each year [1]. MicroRNAs (miRNAs) are a sort of short (18-25 nt) noncoding RNAs that have been proved to be important post-transcriptional regulators of gene expression in cells. They bind to the 3′-untranslated region (3′-UTR) of the mRNA of a specific gene and significantly modulate gene expression, influencing many biological processes [6,7,8]. Aberrant miRNA expression is involved in the pathogenesis and progression of cancers [9, 10] and has the potential to serve as a biomarker for the disease
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.
