Background: Around 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.
Methods: The 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.
Results: Compared 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.
Conclusions: We 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.
Keywords: Cervical cancer; PI3K/Akt; Pten; miR-486-5p.