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Human α-defensin 5 suppressed colon cancer growth by targeting PI3K pathway
Qiao Qiao1, Ruixia Bai2, Wanying Song3
1Department of Obstetrics and Gynecology, Affiliated Hospital of Inner Mongolia Medical University, No.1, Tongdao North Street, Huimin District, Hohhot, 010050, PR China.
Abstract:
Defensins are highly conserved antimicrobial peptides, which ubiquitously expressed in different species. In addition to the functions in host defense, their aberrant expression have also been documented in cancerous tissue including breast cancer, lung caner and renal carcinoma etc. Whereas, roles of Defensin Alpha 5 (DEFA5) in colon cancer has not been explored. Bioinformatic analysis was used to study the expression of DEFA5 and its correlation with clinical outcomes; Western blot, qPCR, Co-immunoprecipitation, xenograft models were used to the study the molecular mechanism. Decreased expression of DEFA5 at protein level was observed in colon tissues. Colon cancer cell lines proliferation and colony formation capacity were significantly suppressed by DEFA5 overexpression. Moreover, in vivo tumor growth in nude mice was also suppressed by DEFA5 overexpression, suggesting a tumor suppressor role of DEFA5 in colon cancer. Mechanistically, DEFA5 directly binds to the subunits of PI3K complex, thus attenuates the downstream signaling transduction, leads to delayed cell growth and metastasis. Collectively, we concluded that DEFA5 showed an inhibitory effect in colon cancer cell growth and may serve as a potential tumor suppressor in colon cancer.
Insights
Defensin Alpha 5 (DEFA5) acts as a tumor suppressor in colon cancer. Overexpression of DEFA5 inhibits cancer cell proliferation, colony formation, and tumor growth by targeting the PI3K signaling pathway.
Area of Science:
- * Molecular biology
- * Oncology
- * Immunology
Background:
- * Defensins are conserved antimicrobial peptides with roles in host defense.
- * Aberrant defensin expression is linked to various cancers, but DEFA5's role in colon cancer is unexplored.
- * Understanding DEFA5's function is crucial for developing new colon cancer therapies.
Purpose of the Study:
- * To investigate the expression of Defensin Alpha 5 (DEFA5) in colon cancer.
- * To elucidate the molecular mechanisms underlying DEFA5's role in colon cancer progression.
- * To assess the potential of DEFA5 as a therapeutic target for colon cancer.
Main Methods:
- * Bioinformatic analysis for DEFA5 expression and clinical outcome correlation.
- * In vitro studies using Western blot, qPCR, and cell culture models.
- * In vivo xenograft models in nude mice and co-immunoprecipitation assays.
Main Results:
- * DEFA5 expression was significantly decreased in colon cancer tissues.
- * Overexpression of DEFA5 suppressed colon cancer cell proliferation and colony formation.
- * DEFA5 directly binds to PI3K subunits, inhibiting downstream signaling and reducing tumor growth and metastasis in vivo.
Conclusions:
- * DEFA5 exhibits a tumor suppressor role in colon cancer.
- * DEFA5 inhibits colon cancer cell growth and metastasis by attenuating PI3K signaling.
- * DEFA5 represents a potential therapeutic target for colon cancer treatment.
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