Knockdown of lncRNA HOTAIR sensitizes breast cancer cells to ionizing radiation through activating miR-218

Abstract Radiotherapy is a major therapeutic strategy for breast cancer, while cancer radioresistance remains an obstacle for the successful control of the tumor. Novel radiosensitizing targets are to be developed to overcome radioresistance. Recently, long non-coding RNAs (lncRNAs) were proved to play critical roles in cancer progression. Among all, lncRNA HOTAIR was found to participate in cancer metastasis and chemoresistance. In the present study, we aimed to investigate the radiosensitizing effects of targeting HOTAIR and the underlying mechanism. Our data showed that HOTAIR (HOX antisense intergenic RNA) was up-regulated in breast cancer cells and tissues, and the expression of HOTAIR increased following irradiation. Knockdown of HOTAIR inhibited cell survival and increased cell apoptosis in response to ionizing radiation. Moreover, compared with control group, radiation induced more DNA damage and cell cycle arrest in HOTAIR knockdown cells. Finally, we found that the radiosentizing effects of HOTAIR were related to the up-regulation of miR-218, a ceRNA of HOTAIR. In conclusion, our finding showed that HOTAIR inhibition sensitizes breast cancer cells to ionizing radiation, induced severe DNA damage and activated apoptosis pathways, suggesting a possible role of HOTAIR as a novel target for breast cancer radiosensitization.

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A radiosensitizer, gallotannin-rich extract from Bouea macrophylla seeds, inhibits radiation-induced epithelial-mesenchymal transition in breast cancer cells

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-021-03363-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jiraporn Kantapan ◽

Siwaphon Paksee ◽

Aphidet Duangya ◽

Padchanee Sangthong ◽

Sittiruk Roytrakul ◽

...

Keyword(s):

Breast Cancer ◽

Dna Damage ◽

Cell Death ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Breast Cancer Cell Lines ◽

Mesenchymal Transition ◽

Mammosphere Formation ◽

Radiation Induced

Abstract Background Radioresistance can pose a significant obstacle to the effective treatment of breast cancers. Epithelial–mesenchymal transition (EMT) is a critical step in the acquisition of stem cell traits and radioresistance. Here, we investigated whether Maprang seed extract (MPSE), a gallotannin-rich extract of seed from Bouea macrophylla Griffith, could inhibit the radiation-induced EMT process and enhance the radiosensitivity of breast cancer cells. Methods Breast cancer cells were pre-treated with MPSE before irradiation (IR), the radiosensitizing activity of MPSE was assessed using the colony formation assay. Radiation-induced EMT and stemness phenotype were identified using breast cancer stem cells (CSCs) marker (CD24−/low/CD44+) and mammosphere formation assay. Cell motility was determined via the wound healing assay and transwell migration. Radiation-induced cell death was assessed via the apoptosis assay and SA-β-galactosidase staining for cellular senescence. CSCs- and EMT-related genes were confirmed by real-time PCR (qPCR) and Western blotting. Results Pre-treated with MPSE before irradiation could reduce the clonogenic activity and enhance radiosensitivity of breast cancer cell lines with sensitization enhancement ratios (SERs) of 2.33 and 1.35 for MCF7 and MDA-MB231cells, respectively. Pretreatment of breast cancer cells followed by IR resulted in an increased level of DNA damage maker (γ-H2A histone family member) and enhanced radiation-induced cell death. Irradiation induced EMT process, which displayed a significant EMT phenotype with a down-regulated epithelial marker E-cadherin and up-regulated mesenchymal marker vimentin in comparison with untreated breast cancer cells. Notably, we observed that pretreatment with MPSE attenuated the radiation-induced EMT process and decrease some stemness-like properties characterized by mammosphere formation and the CSC marker. Furthermore, pretreatment with MPSE attenuated the radiation-induced activation of the pro-survival pathway by decrease the expression of phosphorylation of ERK and AKT and sensitized breast cancer cells to radiation. Conclusion MPSE enhanced the radiosensitivity of breast cancer cells by enhancing IR-induced DNA damage and cell death, and attenuating the IR-induced EMT process and stemness phenotype via targeting survival pathways PI3K/AKT and MAPK in irradiated breast cancer cells. Our findings describe a novel strategy for increasing the efficacy of radiotherapy for breast cancer patients using a safer and low-cost natural product, MPSE.

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Regulation of Ionizing Radiation-Induced Adhesion of Breast Cancer Cells to Fibronectin by Alpha5beta1 Integrin

Radiation Research ◽

10.1667/rr13543.1 ◽

2014 ◽

Vol 181 (6) ◽

pp. 650-658 ◽

Cited By ~ 12

Author(s):

Shin Hee Lee ◽

Huiwen Cheng ◽

Ye Yuan ◽

Shiyong Wu

Keyword(s):

Breast Cancer ◽

Ionizing Radiation ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Radiation Induced

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Effect of MMP-2 gene silencing on radiation-induced DNA damage in human normal dermal fibroblasts and breast cancer cells

Genes and Environment ◽

10.1186/s41021-019-0131-x ◽

2019 ◽

Vol 41 (1) ◽

Cited By ~ 1

Author(s):

Gugalavath Shailender ◽

Seema Kumari ◽

Patnala Kiranmayi ◽

Rama Rao Malla

Keyword(s):

Breast Cancer ◽

Dna Damage ◽

Gene Silencing ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Dermal Fibroblasts ◽

Radiation Induced

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Abstract 3740: Ionizing radiation-induced transcriptomic changes in triple-negative breast cancer cells reveal putative mechanisms of treatment resistance

10.1158/1538-7445.sabcs18-3740 ◽

2019 ◽

Author(s):

Victor T. Lin ◽

Tshering D. Lama-Sherpa ◽

Rajeev S. Samant ◽

Lalita A. Shevde

Keyword(s):

Breast Cancer ◽

Ionizing Radiation ◽

Cancer Cells ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Triple Negative ◽

Treatment Resistance ◽

Radiation Induced ◽

Transcriptomic Changes

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α-Lipoic acid prevents the ionizing radiation-induced epithelial-mesenchymal transition and enhances the radiosensitivity in breast cancer cells

European Journal of Pharmacology ◽

10.1016/j.ejphar.2020.172938 ◽

2020 ◽

Vol 871 ◽

pp. 172938 ◽

Cited By ~ 2

Author(s):

Joytirmay Tripathy ◽

Amit Roy Chowdhury ◽

Monica Prusty ◽

Kartik Muduli ◽

Nilima Priyadarshini ◽

...

Keyword(s):

Breast Cancer ◽

Ionizing Radiation ◽

Cancer Cells ◽

Lipoic Acid ◽

Breast Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Radiation Induced

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Role of Estrogen Receptor Signaling in Breast Cancer Metastasis

International Journal of Breast Cancer ◽

10.1155/2012/654698 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 63

Author(s):

Sudipa Saha Roy ◽

Ratna K. Vadlamudi

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Cancer Cells ◽

Cancer Progression ◽

Breast Cancer Cells ◽

Molecular Mechanisms ◽

Cancer Metastasis ◽

Metastatic Breast ◽

Estrogen Signaling

Metastatic breast cancer is a life-threatening stage of cancer and is the leading cause of death in advanced breast cancer patients. Estrogen signaling and the estrogen receptor (ER) are implicated in breast cancer progression, and the majority of the human breast cancers start out as estrogen dependent. Accumulating evidence suggests that ER signaling is complex, involving coregulatory proteins and extranuclear actions. ER-coregualtory proteins are tightly regulated under normal conditions with miss expression primarily reported in cancer. Deregulation of ER coregualtors or ER extranuclear signaling has potential to promote metastasis in ER-positive breast cancer cells. This review summarizes the emerging role of ER signaling in promoting metastasis of breast cancer cells, discusses the molecular mechanisms by which ER signaling contributes to metastasis, and explores possible therapeutic targets to block ER-driven metastasis.

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DOCK1 Regulates Growth and Motility through the RRP1B-Claudin-1 Pathway in Claudin-Low Breast Cancer Cells

Cancers ◽

10.3390/cancers11111762 ◽

2019 ◽

Vol 11 (11) ◽

pp. 1762 ◽

Cited By ~ 1

Author(s):

Chiang ◽

Chang ◽

Chen ◽

Chang

Keyword(s):

Breast Cancer ◽

Cell Viability ◽

Cancer Cells ◽

Cancer Progression ◽

Breast Cancer Cells ◽

Dna Methyltransferase ◽

Cancer Metastasis ◽

Metastatic Potential ◽

Significant Inhibition ◽

And Migration

Dedicator of cytokinesis 1 (DOCK1) is a critical regulator of cancer metastasis. Claudins are transmembrane proteins that play a role in epithelial barrier integrity. Due to a loss or low expression of claudins (CLDN), the claudin-low type of triple-negative breast cancer (TNBC) is characterized by a mesenchymal-like phenotype with strong metastatic potential. In order to elucidate the mechanism of DOCK1 in cancer metastasis, we first analyzed the transcriptomic changes using a clinical database of human TNBC and found that the increase in DOCK1 expression was highly correlated with the poor survival rate of TNBC patients. Interference with DOCK1 expression by shRNA resulted in re-expression of claudin-1 in conjunction with significant inhibition of cell viability and motility of claudin-low breast cancer cells. Accordingly, overexpression of claudin-1 suppressed cell viability and migration. Genetic knockdown and pharmacological blockade of Rac1/Rac2 up-regulated claudin-1. DOCK1 knockdown also caused a decrease in DNA methyltransferase (DNMT) expression and an increase in claudin-1 transcript and promoter activity. Furthermore, RRP1B mediated DOCK1 depletion, which up-regulated claudin-1 expression, cell viability, and motility in claudin-low breast cancer cells. This study demonstrated that DOCK1 mediates growth and motility through down-regulated claudin-1 expression via the RRP1BDNMTclaudin-1 pathway and that claudin-1 serves as an important effector in DOCK1-mediated cancer progression and metastasis in claudin-low breast cancer cells.

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