MicroRNA-22 inhibits proliferation, invasion and metastasis of breast cancer cells through targeting truncated neurokinin-1 receptor and ERα

Liu, Xiaobin; Zhang, Lufang; Tong, Yingna; Yu, Man; Wang, Meng; Dong, Dong; Shao, Jie; Zhang, Fei; Niu, Ruifang; Zhou, Yunli

doi:10.1016/j.lfs.2018.11.057

Cited by 18 publications

(10 citation statements)

References 34 publications

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“…miRNAs, a class small endogenous noncoding RNAs, play key roles in multiple biological processes by negatively regulating downstream gene expression (7,11). Several miRNAs have been reported to directly target ESR1 to influence breast cancer development and progression, such as miR-22 (12), miR-301a-3p (6), and miR-206 (27). However, there are few studies about miRNAs regulated by ESR1.…”

Section: Discussionmentioning

confidence: 99%

“…To date, several studies have reported that miRNAs directly or indirectly influence expression of ERα, thus involving in regulating growth, invasion, metastasis, and sensitivity of endocrine therapy in breast cancer. For example, miR-22 was found to inhibit breast cancer progression by directly targeting ESR1 (12); miR-873 enhanced tamoxifen sensitivity via indirect suppression of transcriptional activity of ERα by targeting CDK3 which is key for phosphorylating ERα (13); miR-142-3p acted as a tumor suppressor in ER-positive breast cancer by targeting ESR1 (14). However, to the best of our knowledge, reports regarding miRNAs and their target genes regulated by ERα in breast cancer, especially ERα positive breast cancer, remain absent.…”

Section: Introductionmentioning

confidence: 99%

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microRNA-Dependent Modulation of Genes Contributes to ESR1's Effect on ERα Positive Breast Cancer

2020

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Background: Dysregulation of ESR1 accounts for endocrine therapy resistance and metastasis of ERα positive breast cancer. However, the underlying molecular mechanism of ESR1 in ERα positive breast cancer remains insufficiency. Notably, to date, a comprehensive miRNA-mRNA regulatory network involved in modulation of ESR1 in development and progression of ERα positive breast cancer is still not established. Methods: Microarray miRNA and mRNA expression profiling from GEO database were used to obtained significant DE-miRNAs and DE-mRNAs in ERα positive breast cancer. Functional enrichment analysis was conducted by Enrichr database. STRING database was utilized to construct protein-protein interaction network, after which hub genes were identified through Cytoscape. Kaplan-Meier plotter was introduced to perform survival analysis. The relationship between ESR1-miRNA or miRNA-target gene pairs were experimentally validated. Results: 74 DE-miRNAs, including 19 upregulated and 55 downregulated miRNAs, and 830 DE-mRNAs, including 359 upregulated and 471 downregulated mRNAs, in ERα positive breast cancer were identified. Potential DE-mRNAs were statistically enriched in several cancer-associated pathways, such as cell cycle and pathway in cancer. Fifty-one hub genes with node degree more than 10 were screened. Twenty-seven of 51 hub genes had significant prognostic values in ERα positive breast cancer. Based on the 27 hub genes, a miRNA-hub gene network, containing 26 miRNAs, was established. Seven of 26 miRNAs were found to possess prognostic predictive roles for patients with ERα positive breast cancer by combination of TCGA and METABRIC data. Intriguingly, ESR1 positively correlated and regulated the 7 miRNAs and the 7 miRNAs inversely correlated and modulated their corresponding downstream targets in MCF-7 and T47D cells, supporting the accuracy of in silico analysis. The relationship between ESR1-miRNA, miRNA-mRNA, or ESR1-mRNA pairs was validated in clinical ERα positive breast cancer. Conclusions: In total, the current findings from this work add substantially to the understanding of ESR1's molecular regulatory mechanism in ERα positive breast cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

microRNA-Dependent Modulation of Genes Contributes to ESR1's Effect on ERα Positive Breast Cancer

2020

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“…It has been reported that overexpression of miR-22 significantly decreased cell proliferation and survival, and induced cell apoptosis in p53-mutated colon cancer cells (19). In addition, miR-22 was shown to target the truncated neurokinin-1 receptor and estrogen receptor-α to suppress the proliferation, invasion and metastasis of breast cancer cells (20). miR-22 was subsequently shown to enhance the radiosensitivity of small cell lung cancer cells through targeting the ATPase, WRN helicase interacting protein 1 (WRNIP1) (21).…”

Section: Microrna-22 Mediates the Cisplatin Resistance Of Osteosarcommentioning

confidence: 99%

MicroRNA‑22 mediates the cisplatin resistance of osteosarcoma cells by inhibiting autophagy via the PI3K/Akt/mTOR pathway

et al. 2020

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Osteosarcoma (OS) is the most common primary malignant tumor of the bone affecting children and adolescents. Chemotherapy is now considered as a standard component of OS treatment, not only for children, but also for adults. However, chemoresistance continues to pose a challenge to therapy. Inhibition of autophagy has been demonstrated to decrease chemoresistance in OS. Moreover, microRNA-22 (miR-22) inhibits autophagy, leading to an improvement in the sensitivity of cisplatin (CDDP) in OS. The aim of the present study was therefore to investigate whether miR-22 could mediate the CDDP resistance of OS cells by inhibiting autophagy via the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. Cell proliferation assay, LC3 flow cytometry assay and monodansylcadaverine staining in MG63 cells and CDDP resistance cells (MG63/CDDP) were performed to explore to role of miR-22 and CDDP in OS chemoresistance. Inoculation of tumor cells in an in vivo model, reverse transcription-quantitative PCR (RT-qPCR) assay, western blot analysis, and immunohistochemistry analysis were performed to investigate the role of miR-22 and CDDP in the PI3K/Akt/mTOR pathway as it is affected by autophagy. The results revealed that miR-22 inhibited the proliferation of MG63 and MG63/CDDP cells, and enhanced the anti-proliferative ability of CDDP in vivo and in vitro. miR-22 mediated the CDDP resistance of OS cells by inhibiting autophagy and decreasing CDDP-induced autophagy via downregulation of the expression of PI3K, Akt, and mTOR at the mRNA level, and the expression of PI3K, phosphorylated (p)-Akt, and p-mTOR at the protein level. It was also convincingly demonstrated that miR-22 mediates the CDDP resistance of OS by inhibiting autophagy via the PI3K/Akt/mTOR pathway. Furthermore, in the MG63 cells that were affected by CDDP, the role of miR-22 was shown to be similar to that of the investigated inhibitor of PI3K (wortmannin) in terms of regulating the PI3K/Akt/mTOR pathway, and wortmannin could also promote the effect of miR-22. Interestingly, CDDP was demonstrated to induce autophagy by inhibiting the PI3K/Akt/mTOR pathway, whereas the pathway was upregulated in the state of chemoresistance. In conclusion, downregulation of the PI3K/Akt/mTOR pathway was shown to assist in the process of preventing chemoresistance.

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“…In fact, the truncated isoform has been related to malignant transformation in colitis-associated cancer [66], and the overexpression of the truncated isoform promoted the malignant transformation of non-tumorigenic cells [57]. The expression of the full-length isoform has been inversely related to the invasiveness, metastasis and proliferation of tumor cells [57], and its downregulation blocked these mechanisms [67]. The up-regulation of the truncated form is important because it is involved in the growth and malignancy of tumor cells and in the synthesis of cytokines with growth-promoting actions, whereas the full-length form promotes a slow growth of tumor cells [68][69][70].…”

Section: Cancer and The Substance P/neurokinin-1 Receptor Systemmentioning

confidence: 99%

The Neurokinin-1 Receptor Antagonist Aprepitant: An Intelligent Bullet against Cancer?

Muñoz

Coveñas

2020

Cancers

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Neurokinin-1 receptor (NK-1R) antagonists exert antitumor action, are safe and do not cause serious side-effects. These antagonists (via the NK-1R) exert multiple actions against cancer: antiproliferative and anti-Warburg effects and apoptotic, anti-angiogenic and antimetastatic effects. These multiple effects have been shown for a broad spectrum of cancers. The drug aprepitant (an NK-1R antagonist) is currently used in clinical practice as an antiemetic. In in vivo and in vitro studies, aprepitant also showed the aforementioned multiple antitumor actions against many types of cancer. A successful combination therapy (aprepitant and radiotherapy) has recently been reported in a patient suffering from lung carcinoma: the tumor mass disappeared and side-effects were not observed. Aprepitant could be considered as an intelligent bullet against cancer. The administration of aprepitant in cancer patients to prevent recurrence and metastasis after surgical procedures, thrombosis and thromboembolism is discussed, as is the possible link, through the substance P (SP)/NK-1R system, between cancer and depression. Our main aim is to review the multiple antitumor actions exerted by aprepitant, and the use of this drug is suggested in cancer patients. Altogether, the data support the reprofiling of aprepitant for a new therapeutic use as an antitumor agent.

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MicroRNA-22 inhibits proliferation, invasion and metastasis of breast cancer cells through targeting truncated neurokinin-1 receptor and ERα

Cited by 18 publications

References 34 publications

microRNA-Dependent Modulation of Genes Contributes to ESR1's Effect on ERα Positive Breast Cancer

microRNA-Dependent Modulation of Genes Contributes to ESR1's Effect on ERα Positive Breast Cancer

MicroRNA‑22 mediates the cisplatin resistance of osteosarcoma cells by inhibiting autophagy via the PI3K/Akt/mTOR pathway

The Neurokinin-1 Receptor Antagonist Aprepitant: An Intelligent Bullet against Cancer?

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