Autocrine/Paracrine Human Growth Hormone-stimulated MicroRNA 96-182-183 Cluster Promotes Epithelial-Mesenchymal Transition and Invasion in Breast Cancer

Zhang, Weijie; Qian, Pengxu; Zhang, Xiao; Zhang, Min; Wang, Hong; Wu, Mingming; Kong, Xiangjun; Tan, Sheng; Ding, Keshuo; Perry, Jo K.; Wu, Zhengsheng; Cao, Yuan; Lobie, Peter E.; Zhu, Tao

doi:10.1074/jbc.m115.653261

Cited by 77 publications

(73 citation statements)

References 55 publications

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“…The identical protective effect of GH was also seen in HCT-8 colorectal cancer cells where recombinant human GH treatment protected the tumor cells against radiation in a dose-dependent manner (183). Mechanisms of chemotherapeutic resistance in cancer includes but are not limited to (i) abundant expression of a repertoire of drug efflux pumps (184,185,186,187), (ii) sequestration of drugs in melanosomes during melanogenesis (188,189), and (iii) upregulation of EMT markers (159,190,191,192,193,194), a critical mechanism of phenotype switch and chemotherapy evasion in several types of cancers(130, 131). Recently, we reported an elaborate GH-GHR dependent mechanism of drug resistance in human melanoma(130, 131), where we attenuated GHR in human melanoma cells leading to direct downregulation of specific drug efflux pumps of the ABC family leading to increased drug efficacy at a lower dose(131).…”

Section: Role Of Gh-ghr In Cancer Therapy Resistancementioning

confidence: 87%

MECHANISMS IN ENDOCRINOLOGY: Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects?

Basu

Qian

Kopchick

2018

European Journal of Endocrinology

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Growth hormone (GH) is produced primarily by anterior pituitary somatotroph cells. Numerous acute human (h) GH treatment and long-term follow-up studies and extensive use of animal models of GH action have shaped the body of GH research over the past 40-50 years. Work on the GH receptor (R) knock-out (GHRKO) mice and results of studies on GH resistant Laron Syndrome (LS) patients have helped define many physiological actions of GH including those dealing with metabolism, obesity, cancer, diabetes, cognition, and aging/longevity. In this review, we have discussed several issues dealing with these biological effects of GH and attempt to answer the question of whether decreased GH action may be beneficial.

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Section: Role Of Gh-ghr In Cancer Therapy Resistancementioning

confidence: 87%

MECHANISMS IN ENDOCRINOLOGY: Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects?

Basu

Qian

Kopchick

2018

European Journal of Endocrinology

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“…BRMS1 is a tumor suppressor (33). It has been verified that the expression of BRMS1 was regulated by miRNAs, and that it is able to inhibit the process of epithelial-mesenchymal transition and invasion in breast cancer (33). BRMS1 also regulates a network of proteins with central roles in cancer metastasis (19,34).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑125a‑5p inhibits invasion and metastasis of gastric cancer cells by targeting BRMS1 expression

Cao

Tan

et al. 2018

Oncol Lett

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Abstract. Accumulating studies have demonstrated microRNAs (miRNAs/miRs) have an important role in multiple processes of human malignant tumor development and progression. Decreased expression of miR-125a-5p has been observed in several types of cancer, including gastric cancer (GC). However, the mechanism and exact function of miR-125a-5p in GC have not been largely elucidated. In the present study, reverse transcription-quantitative polymerase chain reaction indicated that the expression of miR-125a-5p was downregulated in GC tissues and cell lines compared with matched normal tissues (P<0.01) and normal gastric mucosa cell lines (P<0.01), respectively. Moreover, clinical pathological characteristics and Kaplan-Meier analysis indicated that a low expression of miR-125a-5p was not only associated with lymph metastasis, peritoneal dissemination and advanced tumor-node metastasis stage but also affected the prognosis of GC patients. Compared with miR-control-transfected GC cells, markedly decreased migration and invasion was observed in GC cells that overexpress miR-125a-5p. By contrast, increased metastasis and invasion were observed in miR-125a-5p-knocked down cells compared with the control. Furthermore, luciferase reporter assays indicated that breast cancer metastasis suppressor 1 (BRMS1) was a direct target of miR-125a-5p. Notably, a positive correlation between the levels of BRMS1 and miR-125a-5p in GC tissues was observed, and BRMS1 expression was indicated to be regulated by miR-125a-5p in GC cells. In conclusion, miR-125a-5p may act as a tumor suppressor by targeting the metastasis-inhibitory gene, BRMS1. The data suggesting that BRMS1 is a potential target gene of miR-125a-5p, may provide novel insight into miRNA regulation of human gene expression, and a useful target for gene therapy of GC.

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“…miR-194 was first identified as a suppressor gene in the hepatic epithelial cells of mice by inhibiting the metastasis of liver cancer cells (36). In addition, in cancer of the gut (37,38) and kidney (39), miR-194 served a similar inhibitory role.…”

Section: Discussionmentioning

confidence: 99%

“…By contrast, it was suggested that miR-194 served a role in the promotion and progression of breast cancer (9) and pancreatic ductal adenocarcinoma (40). These studies indicated that miR-194 had various target genes (31)(32)(33)(34)(35)(36)(37)(38)(39)(40). Previous studies have demonstrated that miR-194 inhibited cell migration and invasion, which may have contributed to the anti-tumor activity of trastuzumab on HER2-overexpressing breast cancer cells (41,42).…”

Section: Discussionmentioning

confidence: 99%

Promotional effect of microRNA-194 on breast cancer cells via targeting F-box/WD repeat-containing protein 7

et al. 2018

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Abstract. Breast cancer is the most common type of malignant cancer in females. An increasing number of studies have revealed that microRNAs (miR), which belong to a class of small non-coding RNAs, serve an important role in a number of human cancer subtypes. In the present study, the role of miR-194 in breast cancer cells and its underlying mechanisms were investigated. The results demonstrated that the serum levels of miR-194 were significantly higher in patients of the poorly differentiated and well-differentiated groups, compared with in healthy adults. Additionally, the serum level of miR-194 was significantly higher in the poorly differentiated group compared with in the well-differentiated group. In order to further investigate the role of miR-194 in breast cancer cells, the present study transfected two breast cancer cell lines, MCF-7 and MDA-MB-231, with an empty vector (control), miR-194 (overexpression), antagomiR-194 (inhibitor, functional knock down) or antagomiR-194 and miR-194. An MTT assay was performed in order to detect the proliferation of breast cancer cells in the various groups. The results revealed that the overexpression of miR-194 significantly accelerated cell proliferation, whereas the inhibition of miR-194 significantly decelerated the proliferation of MCF-7 and MDA-MB-231 cells. Furthermore, the expression levels of cyclin D and cyclin E were significantly upregulated in miR-194 overexpressing cells, and the expression levels of cyclin D and cyclin E were significantly downregulated in miR-194 inhibited cells, as compared with in control cells. No significant change was observed in the level of proliferation of cells co-transfected with miR-194 and antagomiR-194, compared with in the control cells. According to the hypothesis suggesting possible target genes of miR-194, the present study proposed that F-box/WD repeat-containing protein 7 (Fbxw-7) may be a direct target of miR-194, which was confirmed by a luciferase reporter assay. The present study suggested that miR-194 expression promoted the proliferation of breast cancer cells by targeting Fbxw-7, and may serve as a biomarker and a novel target for breast cancer therapy.

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Autocrine/Paracrine Human Growth Hormone-stimulated MicroRNA 96-182-183 Cluster Promotes Epithelial-Mesenchymal Transition and Invasion in Breast Cancer

Cited by 77 publications

References 55 publications

MECHANISMS IN ENDOCRINOLOGY: Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects?

MECHANISMS IN ENDOCRINOLOGY: Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects?

MicroRNA‑125a‑5p inhibits invasion and metastasis of gastric cancer cells by targeting BRMS1 expression

Promotional effect of microRNA-194 on breast cancer cells via targeting F-box/WD repeat-containing protein 7

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