Histone demethylase JARID1B/KDM5B promotes aggressiveness of non-small cell lung cancer and serves as a good prognostic predictor

Clinical Epigenetics

Chun-Hua Wang¹  Oluwaseun Adebayo Bamodu²  Chi-Tai Yeh²  Wei-Hwa Lee³  Wen-Chien Huang⁴  Liang-Shun Wang⁵  Kuang-Tai Kuo⁵  M. Hsiao⁶ 

[1] Department of Dermatology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation;Department of Medical Research and Education, Shuang Ho Hospital, Taipei Medical University;Department of Pathology, Shuang Ho Hospital, Taipei Medical University;Division of Thoracic Surgery, Department of Surgery, MacKay Memorial Hospital;Division of Thoracic Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University;Genomics Research Center, Academia Sinica;

关键词: JARID1B;    Lung cancer;    Prognosis;    Cancer stem cells;    c-Met;   

DOI  :  10.1186/s13148-018-0533-9

来源: DOAJ

【 摘 要 】

Abstract Background Lung cancer is the leading cause of cancer death worldwide. Recently, epigenetic dysregulation has been known to promote tumor progression and therefore may be a therapeutic target for anticancer therapy. JARID1B, a member of histone demethylases, has been found to be related to tumorigenesis in certain kinds of cancers. However, its biological roles in non-small cell lung cancer (NSCLC) remain largely unclear. Methods We firstly examined the expression of JARID1B in surgical specimens and six NSCLC cell lines. Then, we evaluated the relationship between JARID1B expression and clinicopathologic parameters in 72 NSCLC patients, thereby established its prognostic importance. We subsequently studied the functional roles of JARID1B in tumorigenesis to verify its clinicopathologic significance. Results Our results showed that JARID1B was overexpressed in NSCLC cells and JARID1B overexpression was associated with tumor size, lymph node metastasis, advanced stages, and poor overall survival in NSCLC patients. JARID1B overexpression resulted in increased cell proliferation and formation of tumorspheres and correlated positively with the expression of cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) markers, while the c-Met signaling pathway was actively involved. It also correlated with the strength of resistance to cisplatin and doxorubicin. On the contrary, downregulation of JARID1B expression by applying shRNA or JARID1B inhibitor PBIT reversed these phenomena. Conclusions JARID1B worsens prognosis of NSCLC patients by promotion of tumor aggressiveness through multiple biological facets which were associated with activation of the c-Met signaling, and can be a novel prognostic biomarker and therapeutic target for NSCLC.

【 授权许可】

Unknown