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Long Noncoding RNA TRPM2-AS Promotes the Growth, Migration, and Invasion of Retinoblastoma via miR-497/WEE1 Axis.

ABSTRACT: Long noncoding RNAs (lncRNAs) exhibit vital roles in many types of cancer, including retinoblastoma (RB), the most common primary intraocular malignancy tumor of infancy. A novel lncRNA TRPM2-AS has been demonstrated to be related to multiple cancers; however, its role in RB remains unclear. Here, we aimed to investigate the function of TRPM2-AS in RB. In this study, TRPM2-AS expression in 35 human RB tissues and RB cell lines was detected by real-time PCR. And, the relationship between its expression and clinicopathological characteristics of RB patients was analyzed. RB cells' proliferation, migration, invasion, apoptosis, and cell cycle were explored after silencing TRPM2-AS. The mechanism of TRPM2-AS in RB was focused on miR-497/WEE1 axis. Additionally, the role and mechanism of TRPM2-AS were confirmed in a xenograft mouse model. We found TRPM2-AS expression was enhanced in RB tissues and cells. And, higher TRPM2-AS expression was related to advanced clinical stage and optic nerve invasion in patients. Downregulation of TRPM2-AS significantly inhibited proliferation, migration, and invasion, elevated apoptosis, attenuated G2/M phase arrest in RB cells, and suppressed tumor growth in vivo. TRPM2-AS acted as a ceRNA for miR-497 to positively regulate WEE1 expression. miR-497 inhibitor or WEE1 overexpression dramatically reversed the effects of TRPM2-AS downregulating on the malignant phenotypes of RB cells. Therefore, TRPM2-AS is an oncogenic lncRNA in RB, and it functions largely through the miR-497/WEE1 pathway. Despite the limited sample size, this study indicates that TRPM2-AS may be a candidate target in RB therapies.

SUBMITTER: Li A

PROVIDER: S-EPMC8112210 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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.

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Long Noncoding RNA TRPM2-AS Promotes the Growth, Migration, and Invasion of Retinoblastoma via miR-497/WEE1 Axis.

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