ARSD, a novel ERα downstream target gene, inhibits proliferation and migration of breast cancer cells via activating Hippo/YAP pathway

AbstractAdvanced breast cancer (BC), especially basal like triple-negative BC (TNBC), is a highly malignant tumor without viable treatment option, highlighting the urgent need to seek novel therapeutic targets. Arylsulfatase D (ARSD), localized at Xp22.3, is a female-biased gene due to its escaping from X chromosome inactivation (XCI). Unfortunately, no systematic investigation of ARSD on BC has been reported. In this study, we observed that ARSD expression was positively related to ERα status either in BC cells or tissue specimens, which were associated with good prognosis. Furthermore, we found a set of hormone-responsive lineage-specific transcription factors, FOXA1, GATA3, ERα, directly drove high expression of ARSD through chromatin looping in luminal subtype BC cells. Opposingly, ARSD still subjected to XCI in TNBC cells mediated by Xist, CpG islands methylation, and inhibitory histone modification. Unexpectedly, we also found that ectopic ARSD overexpression could inhibit proliferation and migration of TNBC cells by activating Hippo/YAP pathway, indicating that ARSD may be a molecule brake on ERα signaling pathway, which restricted ERα to be an uncontrolled active status. Combined with other peoples’ researches that Hippo signaling maintained ER expression and ER + BC growth, we believed that there should exist a regulative feedback loop formation among ERα, ARSD, and Hippo/YAP pathway. Collectively, our findings will help filling the knowledge gap about the influence of ARSD on BC and providing evidence that ARSD may serve as a potential marker to predict prognosis and as a therapeutic target.

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MARK4 inhibits Hippo signaling to promote proliferation and migration of breast cancer cells

EMBO Reports ◽

10.15252/embr.201642455 ◽

2017 ◽

Vol 18 (3) ◽

pp. 420-436 ◽

Cited By ~ 44

Author(s):

Emad Heidary Arash ◽

Ahmed Shiban ◽

Siyuan Song ◽

Liliana Attisano

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Hippo Signaling ◽

And Migration ◽

Proliferation And Migration

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LncRNA RNA Component of Mitochondrial RNA-Processing Endoribonuclease Promotes AKT-Dependent Breast Cancer Growth and Migration by Trapping MicroRNA-206

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.730538 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yingdan Huang ◽

Bangxiang Xie ◽

Mingming Cao ◽

Hua Lu ◽

Xiaohua Wu ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Rna Processing ◽

Cancer Development ◽

Mitochondrial Rna ◽

Cancer Cell Growth ◽

Cell Growth And Migration ◽

Downstream Target ◽

And Migration ◽

Proliferation And Migration

The RNA component of mitochondrial RNA-processing endoribonuclease (RMRP) was recently shown to play a role in cancer development. However, the function and mechanism of RMRP during cancer progression remain incompletely understood. Here, we report that RMRP is amplified and highly expressed in various malignant cancers, and the high level of RMRP is significantly associated with their poor prognosis, including breast cancer. Consistent with this, ectopic RMRP promotes proliferation and migration of TP53-mutated breast cancer cells, whereas depletion of RMRP leads to inhibition of their proliferation and migration. RNA-seq analysis reveals AKT as a downstream target of RMRP. Interestingly, RMRP indirectly elevates AKT expression by preventing AKT mRNA from miR-206-mediated targeting via a competitive sequestering mechanism. Remarkably, RMRP endorses breast cancer progression in an AKT-dependent fashion, as knockdown of AKT completely abolishes RMRP-induced cancer cell growth and migration. Altogether, our results unveil a novel role of the RMRP-miR-206-AKT axis in breast cancer development, providing a potential new target for developing an anti-breast cancer therapy.

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Hsa_circ_0005273 regulates YAP1-Hippo signaling pathway by targeting miR-200a-3p to promote breast cancer progression.

10.21203/rs.3.rs-19095/v1 ◽

2020 ◽

Author(s):

Xuehui Wang ◽

Changle Ji ◽

Qifeng Luo ◽

Jiashu Hu ◽

Xiaochong Deng ◽

...

Keyword(s):

Breast Cancer ◽

Signaling Pathway ◽

Cell Lines ◽

Cancer Progression ◽

Luciferase Reporter ◽

Hippo Signaling ◽

Hippo Signaling Pathway ◽

Potential Biomarker ◽

And Migration ◽

Proliferation And Migration

Abstract Background : Hsa_circ_0005273 is a circRNA generated from several exons of PTK2. However, the potential functions of hsa_circ_0005273 in breast cancer remains unknown. Here we aim to explore the role of hsa_circ_0005273 in BC. Methods : We chose miR-200a-3p as the potential target of hsa_circ_0005273. The expression levels of hsa_circ_0005273 and miR-200a-3p were examined in BC tissues compared with adjacent normal tissues by qRT-PCR. To characterize the function of hsa_circ_0005273, experiments of cell proliferation and migration were performed in BC cell lines infected with lentivirus targeting hsa_circ_0005273. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0005273 in BC. Luciferase reporter assay was conducted to confirm the relationship between hsa_circ_0005273 and miR-200a-3p as well as miR-200a-3p andYAP1. Results : Hsa_circ_0005273 is over-expressed in BC tissues and cell lines, whereas miR-200a-3p expression is repressed. Depletion of has_circ_0005273 or upregulation of miR-200a-3p inhibited the proliferation and migration of BC cells in vitro and vivo. Mechanistically, hsa_circ_0005273 upregulated YAP1 by targeting miR-200a-3p and activated Hippo signaling pathway to promote BC progression. Conclusions : Hsa_circ_0005273 regulates the miR-200a-3p/YAP1 axis and activates Hippo signaling pathway to promote BC progression, and it may serve as a potential biomarker and therapeutic target. Keywords : breast cancer, hsa_circ_0005273, miR-200a-3p,YAP1, progression

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HAND2-AS1 Works as a ceRNA of miR-3118 to Suppress Proliferation and Migration in Breast Cancer by Upregulating PHLPP2

BioMed Research International ◽

10.1155/2020/8124570 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16

Author(s):

Guolei Dong ◽

Xiaorui Wang ◽

Yan Jia ◽

Yongsheng Jia ◽

Weipeng Zhao ◽

...

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

Antisense Rna ◽

Migration And Invasion ◽

Downstream Target ◽

Vital Functions ◽

And Migration ◽

Detailed Function ◽

Selection Of ◽

Proliferation And Migration

Large quantities of long noncoding RNAs (lncRNAs) have been verified to exert vital functions in the process of breast cancer (BC). lncRNA heart and neural crest derivatives expressed 2-antisense RNA 1 (HAND2-AS1) was reported to suppress the development of several cancers. However, its detailed function in BC remained unclear. In the current study, HAND2-AS1 was discovered to be low expressed in BC cell lines, and overexpression of HAND2-AS1 could repress proliferation, migration, and invasion but facilitate apoptosis in BC cells. Moreover, HAND2-AS1 was found to act as a sponge of miR-3118 which was detected to be upregulated in BC cell lines. miR-3118 depletion could constrict the progression of BC. HAND-AS1 hindered the course of BC by reducing the expression of miR-3118. Besides, PHLPP2 was treated as a downstream target of miR-3118 under the selection of RNA pull-down assays. HAND2-AS1 inhibited the process of BC by enhancing expression of PHLPP2. In summary, our study testified that HAND2-AS1 suppressed BC growth by targeting the miR-3118/PHLPP2 axis, indicating that HAND2-AS1 could be regarded as a potential target for BC treatment.

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MIR22HG inhibits breast cancer progression by stabilizing LATS2 tumor suppressor

Cell Death and Disease ◽

10.1038/s41419-021-04105-9 ◽

2021 ◽

Vol 12 (9) ◽

Author(s):

Xiaochong Deng ◽

Danrong Ye ◽

Kaiyao Hua ◽

Hongming Song ◽

Qifeng Luo ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Suppressor ◽

Cancer Progression ◽

Noncoding Rna ◽

Normal Breast ◽

Breast Cancer Progression ◽

Large Tumor ◽

Downstream Target ◽

And Migration ◽

Proliferation And Migration

AbstractThe long noncoding RNA called MIR22 host gene (MIR22HG) was previously identified as a tumor suppressor in several cancers. However, the biological function of MIR22HG in breast cancer remains unknown. In this study, we aimed to determine the function and molecular mechanism of MIR22HG in breast cancer progression using transcriptomics and biotechnological techniques. Our results showed that MIR22HG expression was lower in the cancerous tissues than in the paired adjacent normal breast tissues. Additionally, MIR22HG was found to be mainly located in the cytoplasm and acted as a miR-629-5p sponge. Notably, MIR22HG stabilized the expression of large tumor suppressor 2 (LATS2), which promoted the LATS2-dependent phosphorylation of YAP1 and suppressed the expression of its downstream target oncogenes, thereby inhibiting the proliferation and migration of breast cancer cells. Therefore, our findings reveal the MIR22HG-dependent inhibition of breast cancer cell proliferation and migration via the miR-629-5p/LATS2 pathway, providing new insights and identifying novel therapeutic targets for breast cancer treatment.

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SOX4 Serves an Oncogenic Role in the Tumourigenesis of Human Breast Adenocarcinoma by Promoting Cell Proliferation, Migration and Inhibiting Apoptosis

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892815666200212112119 ◽

2020 ◽

Vol 15 (1) ◽

pp. 49-58

Author(s):

Junhe Zhang ◽

Shujie Chai ◽

Xinyu Ruan

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Caspase 3 ◽

Breast Adenocarcinoma ◽

Migration Ability ◽

Expression Levels ◽

Apoptosis Rate ◽

And Migration ◽

Mcf 7 ◽

Proliferation And Migration

Background: Breast cancer is among the most common malignant cancers worldwide, and breast adenocarcinoma in glandular tissue cells has excessive metastasis and invasion capability. However, little is known on the molecular process by which this disease develops and progresses. Objective: In this study, we explored the effects of sex-determining region Y-box 4 (SOX4) protein on proliferation, migration, apoptosis and tumourigenesis of breast adenocarcinoma and its possible mechanisms. Methods: The SOX4 overexpression or knockdown Michigan Cancer Foundation-7 (MCF-7) cell lines were established. Among the SOX4 overexpression or MCF-7 knockdown cell lines, proliferation, migration ability and apoptosis rate were detected. The expression levels of apoptosis-related proteins (Bax and Cleaved caspase-3) were analysed using Western blot. The effect of SOX4 on tumourigenesis was analysed using the clone formation assay in vitro and tumour xenograft experiment in nude mice. Results: Compared with the overexpression of control cells, proliferation and migration ability of SOX4 overexpression cells significantly increased, the apoptosis rate significantly decreased in addition to the expression levels of Bax and Cleaved caspase-3 (P < 0.05). Compared with the knockdown of control cells, proliferation and migration ability of SOX4 knockdown cells significantly decreased, and the apoptosis rate and expression levels of Bax and Cleaved caspase-3 significantly increased (P < 0.05). Clone formation and tumour growth abilities of SOX4 overexpression cells were significantly higher than those of the control cells (P < 0.05), whereas SOX4 knockdown cells had the opposite effect. Conclusion: SOX4 plays an oncogenic role in breast adenocarcinoma tumourigenesis by promoting cell proliferation, migration and inhibiting apoptosis. It can be used as a potential molecular target for breast cancer gene therapy.

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