The LncRNA HOTAIRM1 Promotes Tamoxifen Resistance by Mediating HOXA1 Expression in ER+ Breast Cancer Cells

Kim, Clara Yuri; Oh, Ji Hoon; Lee, Ji Yeon; Kim, Myoung Hee

doi:10.7150/jca.38728

Cited by 38 publications

(32 citation statements)

References 34 publications

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“…Among these ncRNAs, lncRNAs, as the promising molecular markers for forecasting drug resistance of breast cancer, are becoming new targets for treating breast cancer in the future. For example, LOC645166, lncRNA GAS5, and lncRNA H19 regulate adriamycin resistance in breast cancer cells [4,19,20], and lncRNA UCA1 and lncRNA NONHSAT141924 modulates paclitaxel resistance [21,22], while lncRNA HOTAIRM1 and BLACAT1 can induce tamoxifen resistance in ER + breast cancer cells [23,24]. However, all these lncRNAs were identi ed from breast cancer tissue or cell lines, which limits their utilities in the clinic as a dynamic monitoring biomarker.…”

Section: Discussionmentioning

confidence: 99%

Low expression of lncRNA CTB-104H12.5 induces resistance to adriamycin in HER2 negative breast cancer by downregulating GAS7C

Nian

Xue³

et al. 2020

Preprint

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Abstract Background Adriamycin-based neoadjuvant chemotherapy is widely used in HER2- breast cancer patients, however, some patients have no response or acquire resistance to these regimens. Therefore, it is important to screen patients who respond to adriamycin with biomarkers. Methods A human lncRNA microarray analysis followed by a quantitative real-time polymerase chain reaction (qRT-PCR) assay was utilized to identify the differentially expressed lncRNAs. The proliferation viability of cells transfected with or without CTB 104H12.5 was measured by CCK-8 and clone formation assay, cell apoptosis and cell cycle were evaluated by Flow cytometry. And the expression of RNA and proteins was tested by qRT-PCR and Western blot, respectively. Results Ten whole blood samples from HER2- breast cancer patients who received docetaxel combined with adriamycin regimen were enrolled, a human lncRNA microarray analysis showed that the low expression of CTB-104H12.5 was associated unfavorable prognosis. And the mRNA and protein level of CTB-104H12.5 is much lower in MCF-7/ADR cells than that of MCF-7 cells while CTB-104H12.5 knockdown in MCF cells induces cell resistance to adriamycin, while CTB-104H12.5 overexpression in MCF7/ADR cells reversed their resistance to adriamycin. Also, the mRNA and protein levels of GAS7C were associated with CTB-104H12.5. Conclusions Low expression of CTB-10412.5 predicted resistance to adriamycin in HER2 negative breast cancer, which may serve as a potential biomarker to dynamically monitor adriamycin resistance for breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

Low expression of lncRNA CTB-104H12.5 induces resistance to adriamycin in HER2 negative breast cancer by downregulating GAS7C

Nian

Xue³

et al. 2020

Preprint

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“…We speculate that due to increased phosphorylation of EZH2, EZH2 protein levels did not increase as they did with short-term genistein exposure. Recent study has shown that EZH2 was evidently less enriched in TAMR cells [54]. Study has found that that low H3K27me3 level were signi cantly associated with aromatase inhibitor resistance [25].…”

Section: Discussionmentioning

confidence: 99%

ERK-Mediated Phosphorylation of EZH2 Regulates HER2 Expression on Long-term Genistein-induced Acquired Endocrine Resistance in Estrogen-Receptor-Positive Breast Cancer Cells

Hu¹,

Zhou²,

Yang³

et al. 2020

Preprint

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BackgroundGenistein, a soy isoflavones, is the most important phytoestrogens in typical oriental diet. Many studies have shown that genistein at lower concentrations promotes breast cancer cells growth through the estrogen receptor pathway. However, recent research has found that long-term consumption of low doses of genistein results in hormone-independent growth phenotypes of MCF-7 tumors, with increased expression of HER2. Overexpression of HER2 has been causally associated with endocrine therapy resistance in human breast cancer. The mechanism by which prolonged exposure to genistein leads to increased HER2 expression is unclear. Whether genistein-induced HER2 expression is the cause of endocrine resistance remains to be determined. MethodsWe selected the MCF-7 and T47D breast cancer cells model with higher ERα and lower HER2. It was investigated whether prolonged exposure to genistein induced TAM-sensitive breast cancer cells to TAM-refractory cells by increasing HER2 expression. Furthermore, it was explored whether HER2 expression and endocrine resistance were associated with EZH2. ResultsWe found that genistein had estrogen-like effect and inhibited HER2 expression during short-term exposure. However, long-term exposure to genistein induced acquire endocrine resistance, because of increased expression of HER2. During long-term exposure to genistein, the continuous activation of ERK1/2 phosphorylated EZH2 at Ser21, resulting in a decrease of lysine 27 trimethylation. As H3K27me3 level decreased, the expression of IL-6 and IL-8 increased, and HER2 level gradually increased, forming a feedback loop of ERK1/2 / EZH2/ IL-6 and IL-8 / HER2. ConclusionsThese findings indicated that high HER2 expression caused by EZH2 phosphorylation was an important mechanism of endocrine resistance. The study also provided a new insight for genistein-induced acquired endocrine resistance. For breast cancer patients, long-term use of soy supplements has potential health risk. Especially, monitoring dietary exposure to genistein is advisable when treated with tamoxifen.

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“…This indicates that lncRNAs as ceRNAs have profound implication in controlling endocrine response of BC. In addition, a newly published study has demonstrated that lncRNA HOTAIRM1 promotes acquired tamoxifen resistance in BC by interacting with EZH2, thus preventing the PRC2 complex-mediated H3K27me3 of the putative HOXA1 promoter 69 . This study indicates that HOTAIRM1 is a promising therapeutic target for BC patients with tamoxifen resistance.…”

Section: Lncrnas-mediated Bc Resistance In Different Clinical Scenarimentioning

confidence: 99%

Managing therapeutic resistance in breast cancer: from the lncRNAs perspective

et al. 2020

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Breast cancer (BC) is the most common female malignancy and the second leading cause of cancer-related death worldwide. In spite of significant advances in clinical management, the mortality of BC continues to increase due to the frequent occurrence of treatment resistance. Intensive studies have been conducted to elucidate the molecular mechanisms underlying BC therapeutic resistance, including increased drug efflux, altered drug targets, activated bypass signaling pathways, maintenance of cancer stemness, and deregulated immune response. Emerging evidence suggests that long noncoding RNAs (lncRNAs) are intimately involved in BC therapy resistance through multiple modes of action. Therefore, an in-depth understanding of the implication of lncRNAs in resistance to clinical therapies may improve the clinical outcome of BC patients. Here, we highlight the role and underlying mechanisms of lncRNAs in regulating BC treatment resistance with an emphasis on lncRNAs-mediated resistance in different clinical scenarios, and discuss the potential of lncRNAs as novel biomarkers or therapeutic targets to improve BC therapy response.

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The LncRNA HOTAIRM1 Promotes Tamoxifen Resistance by Mediating HOXA1 Expression in ER+ Breast Cancer Cells

Cited by 38 publications

References 34 publications

Low expression of lncRNA CTB-104H12.5 induces resistance to adriamycin in HER2 negative breast cancer by downregulating GAS7C

Low expression of lncRNA CTB-104H12.5 induces resistance to adriamycin in HER2 negative breast cancer by downregulating GAS7C

ERK-Mediated Phosphorylation of EZH2 Regulates HER2 Expression on Long-term Genistein-induced Acquired Endocrine Resistance in Estrogen-Receptor-Positive Breast Cancer Cells

Managing therapeutic resistance in breast cancer: from the lncRNAs perspective

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