Abstract
BackgroundCervical cancer (CC) is the fourth leading cause of cancer-associated death in women worldwide. Recently, long noncoding RNA (lncRNA) prostate cancer gene expression marker 1 (PCGEM1) has been demonstrated to involve in the initiation and progression of human cancers. However, to date, the clinical and functional significance of PCGEM1 expression in CC progression remains unknown.MethodsqRT-PCR was performed to investigate PCGEM1 expression levels in CC tissues and cell lines. The effect of PCGEM1 on CC cells was assessed by gain- and loss-of-function assays. MS2-binding sequences-MS2-binding protein-based RIP assay (MS2-RIP), RNA pull-down and Luciferase reporter assays were performed to investigate the interaction between PCGEM1 and miR-182. The association between miR-182 and F-box and WD repeat domain containing 11 (FBXW11) was verified by luciferase reporter assay. The effect of PCGEM1 on the NF-κB and β-catenin/TCF signaling pathways was determined by luciferase reporter assay.ResultsOur present study showed that PCGEM1 was significantly upregulated in CC tissues and cell lines. Overexpression of PCGEM1 was correlated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node, distant metastasis and poor prognosis in CC patients. Functionally, PCGEM1 promoted cell proliferation, cell cycle progression, migration and invasion, while suppressed cell apoptosis in CC cells. Further mechanistic investigation revealed that PCGEM1 associated with miR-182 and suppressed its expression. PCGEM1 could act as a competing endogenous (ceRNA) of oncogene F-box and WD repeat domain containing 11 (FBXW11) for miR-182 in CC cells. Additionally, PCGEM1 was capable to activate the NF-κB and β-catenin/TCF signaling pathways, which was reversed by inhibition of FBXW11.ConclusionIn conclusion, our findings demonstrated that PCGEM1-miR-182-FBXW11 axis play an important role in CC progression, and indicated a promising therapeutic target for CC patients.
Highlights
Cervical cancer (CC) is the fourth leading cause of cancer-associated death in women worldwide
Our study provides the first evidence of the existence of a prostate cancer gene expression marker 1 (PCGEM1)-miR-182-F-box and WD repeat domain containing 11 (FBXW11) axis, which may be utilized as a promising therapeutic target for CC
PCGEM1 directly interacts with miR‐182 We investigated the mechanism of the effect of PCGEM1 on CC cells
Summary
Cervical cancer (CC) is the fourth leading cause of cancer-associated death in women worldwide. Long noncoding RNA (lncRNA) prostate cancer gene expression marker 1 (PCGEM1) has been demonstrated to involve in the initiation and progression of human cancers. LncRNAs play crucial roles in controlling gene expression involving several cellular processes of human cancers, such as proliferation, migration, invasion, drug resistance, autophagy and angiogenesis [5, 6]. LncRNA prostate cancer gene expression marker 1 (PCGEM1) has been identified as an oncogenic gene in human cancers. PCGEM1 is capable to induce epithelial–mesenchymal transition (EMT) and metastasis via increasing SNAI1 expression in gastric cancer cells [20]. It is unclear whether PCGEM1 exerts similar function in CC tumorigenesis and development
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