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Role of non‑coding RNA intertwined with the Wnt/β‑catenin signaling pathway in endometrial cancer (Review).

ABSTRACT: Endometrial cancer (EC) ranks as the sixth most common malignancy in women around the world. Although low‑grade and early‑stage EC commonly have an excellent prognosis, ~20% of EC patients experience an unfavorable prognosis. Identifying the pathogenesis and novel therapeutic targets may help address this group of patients. Non‑coding (nc)RNAs, such as long non‑coding RNAs (lncRNAs), microRNAs and circular RNAs (circRNAs), have been associated with EC occurrence and development. In addition, the aberrant activation of the Wnt/β‑catenin signaling pathway can promote the proliferation, invasion, migration and epithelial‑to‑mesenchymal transition (EMT) of EC cells. The network of ncRNAs has also been demonstrated to inhibit or activate the Wnt/β‑catenin signaling pathway. In the present review, ncRNAs, the Wnt/β‑catenin signaling pathway, and their crosstalk in EC were summarized and highlighted. This information is expected to provide novel insights into improving the management of EC using RNA as therapeutics.

SUBMITTER: Tian Y

PROVIDER: S-EPMC10308485 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Role of non‑coding RNA intertwined with the Wnt/β‑catenin signaling pathway in endometrial cancer (Review).

Tian Yanpeng Y Lai Tianjiao T Li Zhongkang Z Mao Meng M Jin Yuxi Y Liu Yana Y Guo Ruixia R

Molecular medicine reports 20230623 2

Endometrial cancer (EC) ranks as the sixth most common malignancy in women around the world. Although low‑grade and early‑stage EC commonly have an excellent prognosis, ~20% of EC patients experience an unfavorable prognosis. Identifying the pathogenesis and novel therapeutic targets may help address this group of patients. Non‑coding (nc)RNAs, such as long non‑coding RNAs (lncRNAs), microRNAs and circular RNAs (circRNAs), have been associated with EC occurrence and development. In addition, the ...[more]

PMID: 37350380

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Project description:Rationale: Abnormal Wnt/β-catenin signaling in the endometrium can lead to both embryo implantation failure and severe pathogenic changes of the endometrium such as endometrial cancer and endometriosis. However, how Wnt/β-catenin signaling is regulated in the endometrium remains elusive. We explored possible regulation of Wnt/β-catenin signaling by multi-drug resistance protein 4 (MRP4), a potential target in cancer chemotherapy, and investigated the mechanism. Methods: Knockdown of MRP4 was performed in human endometrial cells in vitro or in a mouse embryo-implantation model in vivo. Immunoprecipitation, immunoblotting and immunofluorescence were used to assess protein interaction and stability. Wnt/β-catenin signaling was assessed by TOPflash reporter assay and quantitative PCR array. Normal and endometriotic human endometrial tissues were examined. Data from human microarray or RNAseq databases of more than 100 participants with endometriosis, endometrial cancer or IVF were analyzed. In vitro and in vivo tumorigenesis was performed. Results: MRP4-knockdown, but not its transporter-function-inhibition, accelerates β-catenin degradation in human endometrial cells. MRP4 and β-catenin are co-localized and co-immunoprecipitated in mouse and human endometrium. MRP4-knockdown in mouse uterus reduces β-catenin levels, downregulates a series of Wnt/β-catenin target genes and impairs embryo implantation, which are all reversed by blocking β-catenin degradation. Analysis of human endometrial biopsy samples and available databases reveals significant and positive correlations of MRP4 with β-catenin and Wnt/β-catenin target genes in the receptive endometrium in IVF, ectopic endometriotic lesions and endometrial cancers. Knockdown of MRP4 also inhibits in vitro and in vivo endometrial tumorigenesis. Conclusion: A previously undefined role of MRP4 in stabilizing β-catenin to sustain Wnt/β-catenin signaling in endometrial cells is revealed for both embryo implantation and endometrial disorders, suggesting MRP4 as a theranostic target for endometrial diseases associated with Wnt/β-catenin signaling abnormality.

Dataset Information

Role of non‑coding RNA intertwined with the Wnt/β‑catenin signaling pathway in endometrial cancer (Review).

Publications

Role of non‑coding RNA intertwined with the Wnt/β‑catenin signaling pathway in endometrial cancer (Review).

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