Recent research has found that long noncoding RNAs (lncRNAs) were involved in various human cancers. However, the role of these lncRNAs in cervical cancer remains unexplored. Therefore, we aimed to investigate the biological function of maternally expressed gene 3 (MEG3), a cancer-related lncRNA, and its underlying mechanism in cervical cancer. In this study, MEG3 expression of 108 patients' cervical cancer tissues and adjacent normal tissues was detected by quantitative real-time PCR analysis (qRT-PCR), and the functional effect of MEG3 was determined in vitro assays. We observed that MEG3 was downregulated in cervical cancer tissues, compared to the adjacent normal tissues, and was negatively related with FIGO stages, tumor size, lymphatic metastasis, HR-HPV infection and the expression of homo sapiens microRNA-21 (miR-21). Furthermore, we focused on the function and molecular mechanism of MEG3, finding that overexpression of MEG3 reduced the level of miR-21-5p expression, causing inhibition of proliferation and increased apoptosis in cervical cancer cells. In summary, our findings indicate that MEG3 function as a tumor suppressor by regulating miR-21-5p, resulting in the inhibition of tumor growth in cervical cancer. As a result, this study improves our understanding of the function of MEG3 in cervical cancer and will help to provide new potential target sites for cervical cancer treatment.Abbreviations: lncRNA, long noncoding RNA; MEG3, maternally expressed gene 3; qRT-PCR, quantitative real-time PCR analysis; miR-21, homo sapiens microRNA-21; ncRNA, noncoding RNA; NSCLC, nonsmall cell lung cancer; miRNA, MicroRNA; PDCD4, programmed cell death 4; CASC2, cancer susceptibility candidate 2; GAS5, growth arrest specific 5; LVSI, Lymphatic vascular space invasion; MDM2, mouse double minute 2 homolog; SDS-PAGE, SDS-polyacrylamide gel electrophoresis; CCK-8, Cell Counting Kit-8.

Graphical AbstractHighlights d HFS triggers synaptic plasticity of CGRP afferents and chronic pain d LTP-inducible HFS activates spinal microglia through CSF1 signaling d Microglial BDNF is essential for HFS-induced spinal LTP and chronic pain SUMMARY Spinal long-term potentiation (LTP) at C-fiber synapses is hypothesized to underlie chronic pain. However, a causal link between spinal LTP and chronic pain is still lacking. Here, we report that high-frequency stimulation (HFS; 100 Hz, 10 V) of the mouse sciatic nerve reliably induces spinal LTP without causing nerve injury. LTP-inducible stimulation triggers chronic pain lasting for more than 35 days and increases the number of calcitonin gene-related peptide (CGRP) terminals in the spinal dorsal horn. The behavioral and morphological changes can be prevented by blocking NMDA receptors, ablating spinal microglia, or conditionally deleting microglial brain-derived neurotrophic factor (BDNF). HFS-induced spinal LTP, microglial activation, and upregulation of BDNF are inhibited by antibodies against colony-stimulating factor 1 (CSF-1). Together, our results show that microglial CSF1 and BDNF signaling are indispensable for spinal LTP and chronic pain. The microglia-dependent transition of synaptic potentiation to structural alterations in pain pathways may underlie pain chronicity.

BackgroundOur previous study reported that MEG3 is an important tumor suppressor gene that is inactivated in cervical cancer. However, the diagnostic and prognostic values of MEG3, as well as the molecular mechanism of MEG3 inactivation in cervical cancer, remain unclear. In this study, we aimed to further elucidate the role and potential inactivation mechanism of MEG3 in cervical cancer.MethodsROC curve and Cox regression analyses were used to assess the diagnostic and prognostic value of MEG3 in patients with cervical cancer. The methylation status of the MEG3 promoter in cervical cancer tissue samples was tested using methylation-specific PCR. Furthermore, we altered the methylation status of the MEG3 promoter in two cervical cancer cell lines (HeLa and CaSki) using a DNA methylation transfer enzyme inhibitor (5-Aza-CdR), to investigate whether promoter hypermethylation is a potential cause of MEG3 inactivation. Finally, we used CCK-8 and colony formation assays to evaluate the cell proliferation ability of HeLa and CaSki cells that had been treated with 5-aza-CdR, to investigate whether downregulation of MEG3 caused by promoter hypermethylation had biological effects.ResultsROC curve analysis indicated that MEG3 status showed sufficient sensitivity and specificity for prediction of tumor size and lymph node metastasis in patients with cervical cancer. In addition, our follow-up data showed that low MEG3 expression was correlated with recurrence and short overall survival. Moreover, hypermethylation of the MEG3 promoter was observed in most cervical cancer tissue samples, and demethylation of the MEG3 promoter led to re-expression of MEG3 and inhibited proliferation of HeLa and CaSki cells.Conclusions MEG3 is a powerful tool for diagnosis and prognosis of patients with cervical cancer, and low expression of MEG3 is likely to be related to promoter hypermethylation in cervical cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0472-2) contains supplementary material, which is available to authorized users.