LncRNA MNX1‐AS1 promotes the progression of cervical cancer through activating MAPK pathway

Abstract

Long noncoding RNAs (lncRNAs) have been discovered as significant regulators in a wide range of human cancers. Among them, lncRNA MNX1-AS1 has been proved to be an oncogene in ovarian cancer and glioblastoma. However, the regulatory mechanism of MNX1-AS1 in cervical cancer remains to be understood. Therefore, this study planned to explore the role of MNX1-AS1 in cervical cancer. In the beginning, we found that the expression of MNX1-AS1 was obviously upregulated in cervical cancer tissues and cell lines. Kaplan-Meier survival analysis revealed that patients with higher MNX1-AS1 expression level suffered from shorter overall survival time than those with lower MNX1-AS1 level. Moreover, by loss-of-function and gain-of-function assay, the effect of MNX1-AS1 on cell proliferation and apoptosis was examined on cellular level. Results showed that the proliferation of Hela cells was significantly inhibited and apoptosis enhanced by the transfection of shMNX1-AS1, while overexpressing MNX1-AS1 in E6E7 cells presented the contrary results. As for mechanism investigation, it was demonstrated that overexpression of MNX1-AS1 significantly improved the expression of p-ERK1/2 and p-JNK. And the effects of MNX1-AS1 on cell proliferation and apoptosis would be diminished after inactivating the phosphorylation of either ERK or JNK. Taken together, it was identified that MNX1-AS1 promoted proliferation and inhibited apoptosis of cervical cancer cells through MAPK pathway. Highlights 1. Expression of MNX1-AS1 is upregulated in cervical cancer tissues and cell lines.2. MNX1-AS1 expression is of important clinical significance and it is a novel prognosis biomarker in cervical cancer. 3. MNX1-AS1 regulates cell survival, proliferation, and apoptosis in cervical cancer cells. 4. MNX1-AS1 affects the progression of cervical cancer via MAPK pathway. K E Y W O R D S apoptosis, cervical cancer, MAPK pathway., MNX1-AS1, proliferation J Cell Biochem. 2019;120:4268-4277. wileyonlinelibrary.com/journal/jcb 4268 |

The prognostic utility and clinical outcomes of MNX1-AS1 expression in cancers: a systematic review and meta-analysis

“…A total of 882 patients from the all eligible articles were included to evaluate prognostic value of MNX1-AS1 (presented in Table 1). All articles covered gastric cancer(GC) (n = 3) [8][9][10], lung cancer (LC) (n = 3) [6,20,21], other cancer(n = 3) including: esophageal squamous cell carcinoma (ESCC), cervical cancer (CC), epithelial ovarian cancer (EOC) [14,18,22].…”

“…Moreover, MNX1-AS1 could competitively bind to miRNA to regulate related gene or protein expression [13,23]. Additionally, MNX1-AS1 also activates oncogenic pathways including MAPK, BRF2, and AKT/mTOR pathways [7,18,21]. Taken together, MNX1-AS1 usually regulates with other relevant genes or proteins and cooperates to exert oncogenic functions through involving the carcinogenic signaling pathways.…”

“…Discussion MNX1-AS1, also known as MAYA and CCAT5, is located at chromosome 7q36.3 [6]. Upregulation of MNX1-AS1 expression has been found in a variety of cancers, including gastric cancer [8][9][10], lung cancer [6,20,21], esophageal squamous cell carcinoma [14,15], and estrogen-dependent cancer [7,18,22], etc. MNX1-AS1 play a role of functional oncogene in addition to activating AKT/mTOR pathway and its natural sense transcript MNX1 in breast cancer cells, it also promotes the process of EMT [7].…”

“…Knockdown of MNX1-AS1 might affect the expression of CDK4, cyclin D, Bax, and Bcl-2, which may inhibit proliferation and migration capabilities, and promote apoptosis of ovarian cancer cells [11]. In recent years, some studies have reported that MNX1-AS1 is upregulated in tissues of various cancers, including: hepatocellular carcinoma [12], bladder Cancer [13], esophageal squamous cell carcinoma [14,15], lung cancer [16], prostate cancer [17], cervical cancer [18], etc. As a result, these evidences indicated that MNX1-AS1 overexpression may play a pivotal role in predicting worse or favorable prognosis of cancer patients.…”

<p>Long Non-Coding RNA-NEAT1 Promotes Cell Migration and Invasion via Regulating miR-124/NF-κB Pathway in Cervical Cancer</p>

“…22 Zhu et al 23 have indicated that lncRNA TUSC8 suppresses the invasion and migration of CC cells by miR-641/PTEN axis. Liu et al 24 have reported that lncRNA MNX1-AS1 promotes the proliferation and inhibits the apoptosis of CC cells via MAPK pathway. In this study, we found that lncRNA-NEAT1 promoted the proliferation, migration and invasion of CC cells.…”