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DHX36 plays an oncogenic role in breast cancer progression and invasiveness
Chunli Wei1, Dongmei Xu1,2, Jingliang Cheng1
1Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, 319 Zhongshan Road, Luzhou, 646000, Sichuan Province, China.
Abstract:
DHX36 is an ATP-dependent DNA/RNA helicase that unwinds the guanine-quadruplexes (G4s) of DNA or RNA and regulates their metabolism for key biological functions. Breast cancer is a malignant tumor and effective targeted therapy drugs are limited, even though chemotherapy is generally used. In this study, we found that overexpression of DHX36 promotes breast cancer cell growth, migration, and invasion in vitro, while knocking down or knocking out reversed in vitro and in vivo. Moreover, DHX36 was highly expressed in most clinical breast tumor tissues compared with the matched healthy tissues. Accordingly, higher DHX36 expression correlated with poor recurrence-free survival (RFS) in the patients of breast cancer. These results substantiate that DHX36 might be a diagnostic and prognostic biomarker and is a proto-oncogene that promotes the growth and metastasis of breast cancer. Thus, targeting DHX36-associated G4s in genes, particularly in proto-oncogenes, might be a novel anticancer strategy.
Insights
DHX36, a DNA/RNA helicase, promotes breast cancer growth and metastasis. Targeting DHX36 may offer a new breast cancer treatment strategy, as it serves as a potential biomarker.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Breast cancer therapy faces limitations with current targeted drugs.
- DHX36 (DNA helicase II) is an ATP-dependent helicase involved in unwinding guanine-quadruplexes (G4s) in DNA and RNA.
- The role of DHX36 in breast cancer progression and its potential as a therapeutic target remain largely unexplored.
Purpose of the Study:
- To investigate the role of DHX36 in breast cancer cell proliferation, migration, and invasion.
- To determine the expression levels of DHX36 in clinical breast tumor tissues.
- To evaluate the correlation between DHX36 expression and patient prognosis.
Main Methods:
- In vitro studies involving overexpression, knockdown, and knockout of DHX36 in breast cancer cells.
- In vivo experiments to assess tumor growth and metastasis.
- Analysis of DHX36 expression in clinical breast tumor samples and correlation with recurrence-free survival (RFS).
Main Results:
- Overexpression of DHX36 enhanced breast cancer cell growth, migration, and invasion in vitro.
- DHX36 knockdown or knockout inhibited these processes both in vitro and in vivo.
- DHX36 was significantly overexpressed in breast tumors compared to healthy tissues and correlated with poor RFS.
Conclusions:
- DHX36 acts as a proto-oncogene, promoting breast cancer growth and metastasis.
- DHX36 is a potential diagnostic and prognostic biomarker for breast cancer.
- Targeting DHX36 or its associated G4 structures presents a promising novel anticancer strategy.
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