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.

Cervical cancer is one of the most common types of female malignant tumor. It is well established that radiotherapy (RT) is the first‑line treatment of cervical cancer; however, radioresistance is a substantial obstacle to cervical cancer RT. At present, the mechanism underlying radioresistance remains unclear. Emerging evidence has demonstrated that long non‑coding RNAs (lncRNAs) function as crucial regulators of diverse cancers. Aerobic glycolysis, which is a common phenomenon in cancer cells, is associated with various biological functions, including radioresistance. To the best of our knowledge, the present study is the first to explore the role of the lncRNA urothelial cancer associated 1 (UCA1) in cervical cancer radioresistance. In the present study, irradiation was used to establish irradiation‑resistant (IRR) cells, after which a clonogenic survival assay was used to validate radioresistance, reverse transcription‑quantitative polymerase chain reaction was used to evaluate the expression levels of UCA1 and western blotting was conducted to detect the expression levels of glycolysis‑related proteins. In addition, a glucose/lactate assay kit was used to evaluate glucose/lactate concentrations and cells were transfected with small interfering RNA/pcDNA to regulate the expression of UCA1. Following the establishment of IRR cell lines (SiHa‑IRR and HeLa‑IRR), it was demonstrated that SiHa‑IRR and HeLa‑IRR cells exhibited increased expression levels of UCA1 and enhanced glycolysis. Dysregulation of UCA1 and inhibition of glycolysis affected radioresistance of cervical cancer cells. In addition, the results indicated that UCA1 promoted radioresistance‑associated glycolysis in SiHa‑IRR and HeLa‑IRR cells, with the enzyme hexokinase 2 (HK2) acting as a significant regulator in this process. Inhibiting glycolysis by 2‑DG reversed the effects of UCA1 overexpression on HK2 protein expression and radioresistance in SiHa and HeLa cells. Taken together, these findings suggested that UCA1 may have an important role in regulating radioresistance through the HK2/glycolytic pathway, providing novel potential targets to improve cervical cancer RT.

Methylation alterations of specific genes have recently been identified as diagnostic biomarkers for human cancers. Although MEG3 has been proved to be a tumor suppressor in cervical cancer according to our previous study, the diagnostic value of MEG3 methylation in plasma is still unknown. Therefore, the aim of this study is to identify a novel epigenetic biomarker for cervical cancer. In the current study, the level of MEG3 methylation was evaluated using methylation-specific polymerase chain reaction. The results showed that the level of MEG3 methylation was significantly higher in cervical cancer tissues and patients’ plasmas than those in adjacent normal tissues and plasmas of healthy participants respectively. Moreover, the accuracy was good enough for MEG3 methylation in plasma to discriminate CIN III patients from healthy participants. In addition, MEG3 methylation in plasma also has high discriminating power to predict HR-HPV infection and lymph node metastasis. Furthermore, hypermethylation of MEG3 in plasma was associated with worse recurrence-free and overall survival in cervical cancer patients. In conclusions, MEG3 methylation in plasma can serve as a diagnostic and prognostic biomarker for cervical cancer, providing useful information for clinical management.