Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes, such as cell growth, apoptosis and migration. Although downregulation of lncRNA MEG3 has been identified in several cancers, little is known about its role in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to detect MEG3 expression in clinical ESCC tissues, investigate its biological functions and the endoplasmic reticulum (ER) stress-relative mechanism. MEG3 expression levels were detected by qRT-PCR in both tumor tissues and adjacent non-tumor tissues from 28 ESCC patients. PcDNA3.1-MEG3 recombinant plasmids were constructed and transfected to EC109 cells. Cell growth was analyzed by CCK-8 assay. Cell apoptosis was analyzed by fluorescence microscope and Annexin V/PI assay. The protein expression was determined by western blot analysis. The results showed that MEG3 decreased significantly in ESCC tissues relative to adjacent normal tissues. PcDNA3.1-MEG3 plasmids were successfully constructed and the expression level of MEG3 significantly increased after MEG3 transfection to EC109 cells. Ectopic expression of MEG3 inhibited EC109 cell proliferation and induced apoptosis in vitro. MEG3 overexpression increased the expression of ER stress‑related proteins (GRP78, IRE1, PERK, ATF6, CHOP and cleaved‑caspase-3). Our results first demonstrate that MEG3 is downregulated in ESCC tissues. MEG3 was able to inhibit cell growth and induced apoptosis in EC109 cells, most probably via activation of the ER stress pathway.

Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes. Although downregulation of lncRNA maternally expressed gene 3 (MEG3) has been identified in several types of cancers, little is known concerning its biological role and regulatory mechanism in hepatoma. Our previous studies demonstrated that MEG3 induces apoptosis in a p53-dependent manner. The aim of the present study was to determine whether endoplasmic reticulum (ER) stress is involved in MEG3‑induced apoptosis. Recombinant lentiviral vectors containing MEG3 (Lv‑MEG3) were constructed and transfected into HepG2 cells. A 3‑(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, RT‑PCR, flow cytometry, western blot analysis, immunofluorescence and immunohistochemistry were applied. Transfected HepG2 cells were also transplanted into nude mice, and the tumor growth curves were determined. The results showed that the recombinant lentivirus of MEG3 was transfected successfully into the HepG2 cells and the expression level of MEG3 was significantly increased. Ectopic expression of MEG3 inhibited HepG2 cell proliferation in vitro and in vivo, and also induced apoptosis. Ectopic expression of MEG3 increased ER stress‑related proteins 78‑kDa glucose‑regulated protein (GRP78), inositol‑requiring enzyme 1 (IRE1), RNA‑dependent protein kinase‑like ER kinase (PERK), activating transcription factor 6 (ATF6), C/EBP homologous protein (CHOP), caspase‑3, as well as p53 and NF‑κB expression accompanied by NF‑κB translocation from the cytoplasm to the nucleus. Furthermore, inhibition of NF‑κB with Bay11‑7082 decreased p53 expression in the MEG3‑transfected cells. These results indicate that MEG3 inhibits cell proliferation and induces apoptosis, partially via the activation of the ER stress and p53 pathway, in which NF‑κB signaling is required for p53 activation in ER stress.

Menstrual migraine (MM) has a longer duration and higher drug resistance than non-perimenstrual migraine. Calcitonin gene-related peptide (CGRP) and CGRP receptors are expressed in the peripheral and central nervous systems throughout the trigeminovascular system. The CGRP/CGRP receptor axis plays an important role in sensory physiology and pharmacology. CGRP receptor antagonists and anti-CGRP monoclonal antibodies (mAbs) have shown consistent efficacy and tolerability in the prevention of chronic or episodic migraine and are now approved for clinical use. However, few studies have reported the use of these drugs in MM, and no specific treatment for MM has been approved. This review aimed to shed light on the recent advances in targeting calcitonin gene-related peptides for the treatment of menstrual migraines in PubMed. In this review, we first discuss the axis of the CGRP/CGRP receptor. We then discuss the role of CGRP receptor antagonists and anti-CGRP mAbs in MM treatment. Finally, we discuss the role of the combination of anti-CGRP mAbs and CGRP receptor antagonists in migraine treatment and the drugs that inhibit CGRP release. Altogether, the anti-CGRP mAbs or CGRP receptor antagonists showed good efficacy and safety in the treatment of MM.