scholarly journals Downregulation of LncRNA GAS5 causes trastuzumab resistance in breast cancer

Oncotarget ◽  
2016 ◽  
Vol 7 (19) ◽  
pp. 27778-27786 ◽  
Author(s):  
Wentong Li ◽  
Limin Zhai ◽  
Hui Wang ◽  
Chuanliang Liu ◽  
Jinbao Zhang ◽  
...  
2022 ◽  
Vol 2022 ◽  
pp. 1-7
Author(s):  
Yan Ma ◽  
Lei Yu ◽  
Wenxing Yan ◽  
Ling Qiu ◽  
Jianqiu Zhang ◽  
...  

Radioresistance of breast cancer is a major reason for therapeutic failure and limits further increases in the dose of radiation due to severe adverse effects. Recently, long noncoding RNAs (lncRNAs) have been shown to regulate cancer proliferation, chemoresistance, and radioresistance. Among these lncRNAs, lncRNA GAS5 expression was shown to be downregulated in breast cancer and related to trastuzumab resistance. However, its role in the radiation response is unclear. In this study, we demonstrated that lncRNA GAS5 expression was reduced in irradiated cells and that overexpression of GAS5 reduced cell viability and promoted cell apoptosis after irradiation. Moreover, overexpression of GAS5 resulted in increased G2/M arrest and unrepaired DNA damage, indicating a radiosensitizing role of GAS5 in breast cancer cells. Finally, we found that a GAS5-interacting miRNA, miR-21, reversed the radiosensitizing effects of GAS5 by inhibiting the apoptotic pathway. In conclusion, we found that lncRNA GAS5 sensitized breast cancer cells to ionizing radiation by inhibiting DNA repair and suppressing miR-21, identifying novel targets for breast cancer radiosensitization.


2017 ◽  
Vol 28 ◽  
pp. vii25-vii26
Author(s):  
P. Cabello ◽  
J. Forés ◽  
E. Tormo ◽  
B. Pineda ◽  
A. Adam ◽  
...  

2018 ◽  
Vol 48 (1) ◽  
pp. 194-207 ◽  
Author(s):  
Juan Gu ◽  
Yueping Wang ◽  
Xuedong Wang ◽  
Daoping Zhou ◽  
Xinguo Wang ◽  
...  

Background/Aims: An increasing body of evidence shows that long noncoding RNAs (lncRNAs) are involved in many different cancers. In this study, we aimed to investigate the competing endogenous RNA (ceRNA)-dependent mechanism by which the lncRNA GAS5 contributes to the development of breast cancer. Methods: A total of 68 breast cancer patients were enrolled, and breast cancer and adjacent normal tissues were collected. The human breast cancer cell lines MDA-MB-231, MDA-MB-453, BT549, SK-BR-3 and MCF-7 and human breast cell line MCF10A were utilized in this study. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting were performed to detect expression of relative factors. RNA immunoprecipitation (RIP) was used to evaluate the relationship between GAS5 and miR-23a, and a dual luciferase reporter gene assay was employed to assess the relationship between ATG3 and miR-23a. A subcutaneous xenograft nude mouse model was generated to examine the role of GAS5 and its regulatory pathway in autophagy. Results: GAS5 levels were frequently decreased in breast cancer tissues and cell lines, and its relatively low expression was closely related to a larger tumour size, advanced tumour-node-metastasis (TNM) stage and estrogen receptor-negative (ER-) breast cancer tissues. More importantly, we found that GAS5 promoted autophagy, with enhanced autophagosome formation after GAS5 overexpression. GAS5 was found to act as a microRNA sponge in a pathway that included miR-23a and its target gene ATG3. The GAS5-miR-23a-ATG3 axis significantly regulated autophagy in vivo and in vitro. Conclusions: In summary, we report that the GAS5-miR-23a-ATG3 axis can be regarded as a key regulator of autophagy pathways in breast cancer; it may constitute a promising biomarker and therapeutic target in the future.


2018 ◽  
Vol 22 (10) ◽  
pp. 4935-4947 ◽  
Author(s):  
Huaying Dong ◽  
Wei Wang ◽  
Shaowei Mo ◽  
Qiang Liu ◽  
Xin Chen ◽  
...  

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