P68 RNA Helicase facilitates Breast Cancer progression by promoting Proliferation and Migration via PDGFR-β/AR axis

Long non-coding RNAs (lncRNAs) have been found to participate in multiple genetic pathways in cancer. Also, mitochondria-associated lncRNAs have been discovered to modulate mitochondrial function and metabolism. Previously, we identified oxygen-responsive lncRNAs in MCF-7 breast cancer cells under different oxygen concentrations. Among them, a novel mitochondria-encoded lncRNA, mitochondrial oxygen-responsive transcript 1 (MTORT1), was chosen for further investigation. Nuclear, cytoplasmic, and mitochondrial fractionation assays were performed to evaluate the endogenous expression levels of MTORT1 in breast cancer cells. In vitro proliferation and migration assays were conducted to investigate the functions of MTORT1 in breast cancer cells by knockdown of MTORT1. RNA immunoprecipitation and luciferase reporter assays were used to examine the physical binding between MTORT1 and microRNAs. Our results showed that MTORT1 had low endogenous expression levels in breast cancer cells and was mainly located in the mitochondria. Knockdown of MTORT1 enhanced cell proliferation and migration, implying a tumor suppressor role of this novel mitochondrial lncRNA. MTORT1 served as sponge of miR-26a-5p to up-regulate its target genes, CREB1 and STK4. Our findings shed some light on the characterization, function, and regulatory mechanism of the novel hypoxia-induced mitochondrial lncRNA MTORT1, which functions as a microRNA sponge and may inhibit breast cancer progression. These data suggest that MTORT1 may be a candidate for therapeutic targeting of breast cancer progression.

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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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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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Tripartite motif-containing protein 6 facilitates growth and migration of breast cancer through degradation of STUB1

European Journal of Histochemistry ◽

10.4081/ejh.2021.3214 ◽

2021 ◽

Vol 65 (1) ◽

Author(s):

Chuanchao Wei ◽

Jiayue Wu ◽

Weiyan Liu ◽

Jingfeng Lu ◽

Hongchang Li ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Breast Cancer Progression ◽

Potential Therapeutic Target ◽

Tripartite Motif ◽

And Migration ◽

Breast Cancer Growth

Proteins in the tripartite motif-containing protein (TRIM) family participates in carcinogenesis. However, little attention was focused on the role of TRIM6 on development of breast cancer. Expression level of TRIM6 was found to be markedly enhanced in breast cancer cells and tissues. Functional assays demonstrated that overexpression of TRIM6 promoted breast cancer progression through increase of YAP1 (Yes-associated Protein 1), while knockdown of TRIM6 suppressed in vitro breast cancer progression and in vivo tumor growth through decrease of YAP1. Co-Immunoprecipitation (co-IP) showed that TRIM6 interacted with STUB1 (stress induced phosphoprotein 1 homology and U-box containing protein 1). TRIM6 promoted ubiquitination-mediated degradation of STUB1 to promote YAP1 signaling. Overexpression of STUB1 attenuated TRIM6-induced promotion of breast cancer growth. In conclusion, TRIM6 contributed to breast cancer progression through ubiquitination-dependent proteasomal degradation of STUB1 and provocation of YAP1 pathway, providing potential therapeutic target for breast cancer.

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Macrophage conditioned media promotes adipocyte cancer-association, which in turn stimulates breast cancer proliferation and migration

10.21203/rs.3.rs-253267/v1 ◽

2021 ◽

Author(s):

Dale B. Bosco ◽

Yi Ren ◽

Karin A. Vallega ◽

Qing-Xiang Amy Sang

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Breast Cancer Cells ◽

Conditioned Media ◽

Expression Levels ◽

Cell Counts ◽

And Migration ◽

Promote Breast Cancer ◽

Proliferation And Migration

Abstract Background Breast cancer is the most common cancer in women and the leading cause of female cancer deaths worldwide. Obesity causes chronic inflammation and is a risk factor for post-menopausal breast cancer and poor prognosis. Obesity triggers increased infiltration of macrophages into adipose tissue, yet little research has focused on the effects of macrophages in early stages of breast tumor development in obese patients. In this study, the effects of pro-inflammatory macrophages on breast cancer-adipocyte crosstalk were investigated.Methods An innovative human cell co-culture system was used to model the paracrine interactions among adipocytes, macrophages, and breast cancer cells, and how they facilitate tumor progression. The effects on cancer cells were examined using cell counts and migration assays. Quantitative reverse-transcription polymerase chain reaction was used to measure the expression levels of several cytokines and proteases to analyze adipocyte cancer-association.Results Macrophage conditioned media intensified the effects of breast cancer-adipocyte crosstalk. Adipocytes became delipidated and increased production of pro-inflammatory cytokines, even in the absence of cancer cells, although the expression levels were highest with all three cell components. As a result, co-cultured breast cancer cells became more aggressive, with increased proliferation and migration compared to adipocyte-breast cancer co-cultures treated with unconditioned media.Conclusions Macrophage conditioned media promotes adipocyte cancer-association. These macrophage-adipocyte paracrine interactions promote breast cancer cell proliferation and migration. Thus, macrophages may contribute to adipocyte inflammation and cancer-association and promote breast cancer progression.

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OXER1 and RACK1-associated pathway: a promising drug target for breast cancer progression

Oncogenesis ◽

10.1038/s41389-020-00291-x ◽

2020 ◽

Vol 9 (12) ◽

Author(s):

Mirco Masi ◽

Enrico Garattini ◽

Marco Bolis ◽

Daniele Di Marino ◽

Luisa Maraccani ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Signaling Pathway ◽

Cancer Progression ◽

Drug Target ◽

Cell Proliferation And Migration ◽

Membrane Bound ◽

And Migration ◽

Androgen Effects ◽

Proliferation And Migration

AbstractRecent data indicate that receptor for activated C kinase 1 (RACK1) is a putative prognostic marker and drug target in breast cancer (BC). High RACK1 expression is negatively associated with overall survival, as it seems to promote BC progression. In tumors, RACK1 expression is controlled by a complex balance between glucocorticoids and androgens. Given the fact that androgens and androgenic derivatives can inhibit BC cell proliferation and migration, the role of androgen signaling in regulating RACK1 transcription in mammary tumors is of pivotal interest. Here, we provide evidence that nandrolone (19-nortosterone) inhibits BC cell proliferation and migration by antagonizing the PI3K/Akt/NF-κB signaling pathway, which eventually results in RACK1 downregulation. We also show that nandrolone impairs the PI3K/Akt/NF-κB signaling pathway and decreases RACK1 expression via binding to the membrane-bound receptor, oxoeicosanoid receptor 1 (OXER1). High levels of OXER1 are observed in several BC cell lines and correlate with RACK1 expression and poor prognosis. Our data provide evidence on the role played by the OXER1-dependent intracellular pathway in BC progression and shed light on the mechanisms underlying membrane-dependent androgen effects on RACK1 regulation. Besides the mechanistic relevance, the results of the study are of interest from a translational prospective. In fact, they identify a new and actionable pathway to be used for the design of innovative and rational therapeutic strategies in the context of the personalized treatment of BC. In addition, they draw attention on nandrolone-based compounds that lack hormonal activity as potential anti-tumor agents.

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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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M2 macrophages contribute to cell proliferation and migration of breast cancer

10.21203/rs.3.rs-39373/v1 ◽

2020 ◽

Author(s):

Daoyuan Tu ◽

Jin Dou ◽

Mingkao Wang ◽

Haiwen Zhuang ◽

Xiaoyu Xiaoyu

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cancer Progression ◽

Breast Cancer Cells ◽

M2 Macrophage ◽

M2 Macrophages ◽

Cell Proliferation And Migration ◽

And Migration ◽

Proliferation And Migration

Abstract Background: Breast cancer is a kind of malignant tumor that severely threatens women’s health and life worldwide. Macrophages have been reported to mediate tumor progression, while the potential mechanism still needs further identification.Methods: Human monocytic cell line THP-1 was used to induce M2-macrophage. Real-time PCR and western blot were performed to determine gene expression in mRNA and protein level, respectively. Cell proliferation was determined using MTT assays, while cell migration was detected based on the scratch wound healing assays.Results: The supernatant medium of M2-macrophages incubated breast cancer cells showed increased cell proliferation and reduced expression of IRF-7. Overexpression of IRF-7 reversed the increased level of M2-macrophage induced cell proliferation and migration. The supernatant medium of M2-macrophages incubation promoted miR-1587 expression in breast cancer cells. miR-1587 overexpression promoted cell proliferation and migration of breast cancer. In addition, miR-1587 knockdown suppressed cell proliferation and migration that induced by M2-macrophages. miR-1587 targets IRF-7 to regulate its expression. Knockdown of IRF-7 reversed the effects of miR-1587 knockdown on cell proliferation and migration.Conclusion: Collectively, this study revealed that miR-1587/IRF-7 mediated the mechanism of M2-macrophages-induced breast cancer progression, and this would shed light on the further clinical therapy of breast cancer.

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Usp41, a Potential Candidate Gene in Development of Breast Cancer

10.21203/rs.3.rs-272641/v1 ◽

2021 ◽

Author(s):

rui ling ◽

Meiling Huang ◽

Jian Zhang ◽

Jingjing Xiao ◽

Nanlin Li

Keyword(s):

Breast Cancer ◽

Mass Spectrum ◽

Cancer Progression ◽

Potential Role ◽

Cell Function ◽

Cancer Cell Line ◽

Potential Candidate ◽

Potential Candidate Gene ◽

And Migration ◽

Proliferation And Migration

Abstract Background: Breast cancer is the most common cancer diagnosed among women and is the second leading cause of cancer death. It is of great significance to explore potential candidate targets. Methods: Cell function assays, siRNA, western blot, mass spectrum, flow cytometry, and other molecular biology techniques were conducted to verify the function of USP41 to breast cancer cell line. Results: The results indicate that USP41 (ubiquitin-specific proteases 41) expression is positively related to breast cancer progression. USP41 overexpression greatly enhanced breast cancer colony-forming ability, proliferation and migration. In contrast, USP41 knockdown significantly inhibited breast cancer colony-forming ability, proliferation and migration. Moreover, association of USP41 with RACK1 (Receptor for activated C kinase 1) was proved by mass spectrum, indicating its potential role in TGF-β signaling. Conclusions: USP41 can be a potential therapeutic target against breast cancer via RACK1.

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