scholarly journals miR-221/222 promote tumor growth and suppress apoptosis by targeting lncRNA GAS5 in breast cancer

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Yuanyuan Zong ◽  
Yazhou Zhang ◽  
Xichao Sun ◽  
Tao Xu ◽  
Xiankui Cheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Novel Approach ◽  
Promote Tumor Growth ◽  
Direct Target Gene ◽  
New Perspective ◽  
Cancer Tissues

Abstract MicroRNAs (miRNAs) are 21–23-nucleotide, short, non-coding RNAs that play important roles in virtually all biological pathways in mammals and other multicellular organisms. The association of miR-221 and miR-222 (miR-221/222) for breast cancer is critical, but their detailed roles in its development and progression remain unclear. In the present study, we found that miR-221/222 were consistently up-regulated in breast cancer tissues. We then investigated the molecular mechanisms by which miR-221/222 contributed to breast cancer and identified growth arrest–specific transcript 5 (GAS5) as a direct target gene of miR-221/222. In contrast with the up-regulated expression levels of miR-221/222, GAS5 levels were significantly down-regulated and negatively correlated with miR-221/222 in breast cancer tissues. In addition, we showed that miR-221/222 inhibitors increased cellular apoptosis, miR-221/222 mimics decreased the cell apoptosis in breast cancer cells, and restoration of GAS5 expression attenuated the anti-apoptotic effects of miR-221/222 in breast cancer cells, indicating that GAS5 was a direct mediator of miR-221/222 function. Finally, we showed that miR-221/222 suppressed GAS5 expression significantly and enhanced tumor growth in a mouse model of breast cancer xenografts. The present study highlighted the important role of miR-221/222 as oncomiRs in breast cancer, which inhibited GAS5 translation. These findings may provide a new perspective for the molecular mechanism of breast carcinogenesis and provide a novel approach to the treatment of breast cancer.

scholarly journals ZFHX3 Promotes the Proliferation and Tumor Growth of ER-Positive Breast Cancer Cells Likely by Enhancing Stem-Like Features and MYC and TBX3 Transcription

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3415
Author(s):  
Ge Dong ◽  
Gui Ma ◽  
Rui Wu ◽  
Jinming Liu ◽  
Mingcheng Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Mammary Epithelial Cells ◽  
Progesterone Receptors ◽  
Mammary Epithelial ◽  
Luciferase Reporter ◽  
Mammosphere Formation

Breast cancer is a common malignancy, but the understanding of its cellular and molecular mechanisms is limited. ZFHX3, a transcription factor with many homeodomains and zinc fingers, suppresses prostatic carcinogenesis but promotes tumor growth of liver cancer cells. ZFHX3 regulates mammary epithelial cells’ proliferation and differentiation by interacting with estrogen and progesterone receptors, potent breast cancer regulators. However, whether ZFHX3 plays a role in breast carcinogenesis is unknown. Here, we found that ZFHX3 promoted the proliferation and tumor growth of breast cancer cells in culture and nude mice; and higher expression of ZFHX3 in human breast cancer specimens was associated with poorer prognosis. The knockdown of ZFHX3 in ZFHX3-high MCF-7 cells decreased, and ZFHX3 overexpression in ZFHX3-low T-47D cells increased the proportion of breast cancer stem cells (BCSCs) defined by mammosphere formation and the expression of CD44, CD24, and/or aldehyde dehydrogenase 1. Among several transcription factors that have been implicated in BCSCs, MYC and TBX3 were transcriptionally activated by ZFHX3 via promoter binding, as demonstrated by luciferase-reporter and ChIP assays. These findings suggest that ZFHX3 promotes breast cancer cells’ proliferation and tumor growth likely by enhancing BCSC features and upregulating MYC, TBX3, and others.

LncRNA NEAT1 accelerates breast cancer progression through regulating miR-410-3p/ CCND1 axis

2020 ◽  
Vol 29 (2) ◽  
pp. 277-290
Author(s):  
Xuan Liu ◽  
Weirong Yao ◽  
Haiwei Xiong ◽  
Qiang Li ◽  
Yingliang Li
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Breast Cancer Progression ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Cancer Tissues

BACKGROUND: Breast cancer is the most common malignant tumor and usually occurs in women. Studies have shown that lncRNA nuclear enriched abundant transcript 1 (NEAT1) contributes to breast cancer progression. This study intends to further investigate the molecular mechanism of NEAT1 in breast cancer. METHODS: The expression levels of NEAT1, miR-410-3p and Cyclin D1 (CCND1) were detected by quantitative real-time PCR (qRT-PCR) in breast cancer tissues and cells. Kaplan-Meier analysis and the log-rank test were performed to determine the relationship between NEAT1 and overall survival. Cell Counting Kit-8 (CCK-8) assay analyzed cell proliferation. Transwell assay was performed to examine cell migration and invasion. The protein levels of CCND1 and epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin and Vimentin) were measured by western blot. The target relationship was predicted by bioinformatics analysis, and confirmed by luciferase reporter assay and RNA Immunoprecipitation (RIP) assay. Xenograft analysis was used to evaluate the tumor growth in vivo. RESULTS: NEAT1 and CCND1 were upregulated, while miR-410-3p was down-regulated in breast cancer tissues and cells. Higher NEAT1 expression level was associated with lower survival rate of breast cancer patients. Knockdown of miR-410-3p restored silenced NEAT1-mediated the inhibition of on proliferation, migration, invasion and EMT of breast cancer cells. In addition, NEAT1 regulated CCND1 expression by sponging miR-410-3p in breast cancer cells. NEAT1 knockdown blocked the tumor growth in vivo. CONCLUSION: NEAT1 induced breast cancer progression by regulating the miR-410-3p/CCND1 axis, indicating that NEAT1 may be a potential therapeutic target in breast cancer.

scholarly journals Exosomal PD-L1 harbors active defense function to suppress T cell killing of breast cancer cells and promote tumor growth

Cell Research ◽  
2018 ◽  
Vol 28 (8) ◽  
pp. 862-864 ◽  
Author(s):  
Yi Yang ◽  
Chia-Wei Li ◽  
Li-Chuan Chan ◽  
Yongkun Wei ◽  
Jung-Mao Hsu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cell Killing ◽  
Active Defense ◽  
Promote Tumor Growth ◽  
Defense Function

scholarly journals Hypoxia-Induced MALAT1 Promotes the Proliferation and Migration of Breast Cancer Cells by Sponging MiR-3064-5p

2021 ◽  
Vol 11 ◽  
Author(s):  
Chung-Hsien Shih ◽  
Li-Ling Chuang ◽  
Mong-Hsun Tsai ◽  
Li-Han Chen ◽  
Eric Y. Chuang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Cellular Migration ◽  
Expression Levels ◽  
Promote Tumor Growth ◽  
Rna Immunoprecipitation ◽  
And Migration

Hypoxia, a common process during tumor growth, can lead to tumor aggressiveness and is tightly associated with poor prognosis. Long noncoding RNAs (lncRNAs) are long ribonucleotides (>200 bases) with limited ability to translate proteins, and are known to affect many aspects of cellular function. One of their regulatory mechanisms is to function as a sponge for microRNA (miRNA) to modulate its biological functions. Previously, MALAT1 was identified as a hypoxia-induced lncRNA. However, the regulatory mechanism and functions of MALAT1 in breast cancer are still unclear. Therefore, we explored whether MALAT1 can regulate the functions of breast cancer cells through miRNAs. Our results showed the expression levels of MALAT1 were significantly up-regulated under hypoxia and regulated by HIF-1α and HIF-2α. Next, in contrast to previous reports, nuclear and cytoplasmic fractionation assays and fluorescence in situ hybridization indicated that MALAT1 was mainly located in the cytoplasm. Therefore, the labeling of MALAT1 as a nuclear marker should be done with the caveat. Furthermore, expression levels of miRNAs and RNA immunoprecipitation using antibody against AGO2 showed that MALAT1 functioned as a sponge of miRNA miR-3064-5p. Lastly, functional assays revealed that MALAT1 could promote cellular migration and proliferation of breast cancer cells. Our findings provide evidence that hypoxia-responsive long non-coding MALAT1 could be transcriptionally activated by HIF-1α and HIF-2α, act as a miRNA sponge of miR-3064-5p, and promote tumor growth and migration in breast cancer cells. These data suggest that MALAT1 may be a candidate for therapeutic targeting of breast cancer progression.

scholarly journals Long Non-Coding RNA SNHG19 Promotes Breast Cancer Progression by Regulating miR-299-5p

2021 ◽  
Author(s):  
Hongquan Lu ◽  
Zhenjia Jiang
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Tissues

Abstract Background: Accumulating evidence has suggested that long noncoding RNA (lncRNA) played crucial roles in the development of human malignances including breast cancer. SNHG19 is a newly identified lncRNA which exerted oncogenic function in non-small cell lung cancer, but whether SNHG19 was involved the development of other cancer, such as breast cancer still unclear. Methods: qRT-PCR was performed to examine the expression of SNHG19 and miR-299-5p in breast cancer tissues and cell lines. Cell proliferation was measure using CCK-8 and colony formation assay. Cell migration and invasion ability was detected by wound healing assay and transwell invasion assay. Bioinformatics analysis, dual luciferase reporter assay, RIP assay and Pull down assay were used to verify the direct binding between SNHG19 and miR-299-5p. The xenotransplantation mouse model was established to explore the effect of SNHG19 on breast cancer tumor growth in vivo.Results: We found that SNHG19 expression level was up-regulated in breast cancer tissues and cell lines, while miR-299-5p expression was down-regulated in breast cancer tissues and it was negatively correlated with SNHG19 expression. Silence of SNHG19 inhibited breast cancer cells proliferation, migration and invasion in vitro. Moreover, SNHG19 knockdown suppressed tumor growth of breast cancer cells in vivo. Mechanistically, SNHG19 acted as a ceRNA (competitive endogenous RNA) to sponge miR-299-5p. Finally, the rescue assays further confirmed that miR-299-5p inhibitor reversed the inhibitory effects of SNHG19 knockdown on breast cancer cell proliferation, migration and invasion.Conclusions: In conclusion, our findings proved that SNHG19 promoted breast cancer progression via sponging miR-299-5p and might function as promising prognostic indicator and therapeutic target for breast cancer.

Estrogen-induced factors of breast cancer cells partially replace estrogen to promote tumor growth

Science ◽  
1986 ◽  
Vol 232 (4757) ◽  
pp. 1540-1543 ◽  
Author(s):  
R. Dickson ◽  
M. McManaway ◽  
M. Lippman
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Promote Tumor Growth

scholarly journals ZMYND8 expression in breast cancer cells blocks T-lymphocyte surveillance to promote tumor growth

2020 ◽  
pp. canres.1710.2020
Author(s):  
Yong Wang ◽  
Maowu Luo ◽  
Yan Chen ◽  
Yijie Wang ◽  
Bo Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
T Lymphocyte ◽  
Breast Cancer Cells ◽  
Promote Tumor Growth

scholarly journals Tumor cell-adipocyte gap junctions activate lipolysis and are essential for breast tumorigenesis

2018 ◽  
Author(s):  
Roman Camarda ◽  
Jeremy Williams ◽  
Serghei Malkov ◽  
Lisa J. Zimmerman ◽  
Suzanne Manning ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Gap Junctions ◽  
Gap Junction ◽  
Cancer Cells ◽  
Breast Tumor ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Dependent Manner

AbstractDuring tumorigenesis, a heterotypic interface exists between cancer and stromal cells that can both support and repress tumor growth. In the breast, studies have demonstrated a pro-tumorigenic role for adipocytes. However, the molecular mechanisms by which breast cancer cells coopt adipocytes remain elusive. Studying breast tumors and normal adjacent tissue (NAT) from several patient cohorts and mouse models, we show that lipolysis and lipolytic signaling are activated in NAT. We investigate the tumor-adipocyte interface and find that functional gap junctions form between breast cancer cells and adipocytes. As a result, cAMP, a critical lipolysis-inducing signaling molecule, is transferred from breast cancer cells to adipocytes and activates lipolysis in a gap junction-dependent manner; a fundamentally new mechanism of lipolysis activation in adipocytes. We find that gap junction formation depends upon connexin 31 (Cx31), and that Cx31 is essential for breast tumor growth and activation of lipolysis in vivo. Thus, direct tumor cell-adipocyte interaction is critical for tumorigenesis and may serve as a new therapeutic target in breast cancer.One sentence summaryGap junctions between breast cancer cells and adipocytes transfer cAMP and activate lipolysis in the breast tumor microenvironment.

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