Defensin alpha 6 (DEFA6) is a prognostic marker in colorectal cancer

Article type: Research Article

Authors: Jeong, Dongjun^{a; b} | Kim, Hyeongjoo^b | Kim, Doyeon^b | Ban, Seona^b | Oh, Seunghyun^b | Ji, Sanghee^b | Kang, DongHyun^c | Lee, Hyunyong^c | Ahn, Tae Sung^c | Kim, Han Jo^d | Bae, Sang Byung^d | Lee, Moon Soo^c | Kim, Chang-Jin^a | Kwon, Hyog Young^{e; *} | Baek, Moo-Jun^{c; *}

Affiliations: [a] Department of Pathology, College of Medicine, Soonchunhyang University, Chungcheongnam-do, 330-722, Korea | [b] Soonchunhyang Medical Science Research Institute, College of Medicine, Soonchunhyang University, Chungcheongnam-do, 330-722, Korea | [c] Department of Surgery, College of Medicine, Soonchunhyang University, Chungcheongnam-do, 330-723, Korea | [d] Department of Oncology, College of Medicine, Soonchunhyang University, Chungcheongnam-do, 330-722, Korea | [e] Soonchunhyang Institute of Medi-bio Science, Soonchunhyang University, Chungcheongnam-do, 31151, Korea

Correspondence: [*] Corresponding authors: Hyog Young Kwon, Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, 25 Bongjeong-ro, Cheonan, Chungcheongnam-do, 31151, Korea. Tel.: +82 41 413 5021; E-mail: hykwon@sch.ac.kr. Moo-Jun Baek, Department of Surgery, College of Medicine, Soonchunhyang University, 31 soonchunhyang 6 gil, Dongnam-gu, Cheonan, Chungcheongnam-do, 330-723, Korea. Tel.: +82 10 7474 1991; Fax: +82 41 570 2546; E-mail: ssurge@sch.ac.kr.

Abstract: Defensin alpha 6 (DEFA6) is a member of the alpha defensin family of microbicidal and cytotoxic peptides that defend against bacteria and viruses. Here, we provide a novel function of DEFA6 in tumorigenesis of colorectal cancer (CRC) in vitro and in vivo. Specifically, DEFA6 is highly expressed in both CRC cancer cell lines as well as patient-derived samples at the level of RNA and protein. By shRNA-mediated loss of function of DEFA6, we found that proliferation, migration, invasion, colony forming ability of CRC cell lines were impaired in the absence of DEFA6 in vitro. Furthermore, DEFA6-deficient cancer cells exhibited significantly reduced growth rates compared to control cells in vivo. More importantly, by analyzing 352 patient-derived samples, we revealed that DEFA6 is associated with overall survival rate of CRC patients and thus an independent prognostic marker for CRC. These results suggest that DEFA6 plays an essential oncogenic role in CRC and serves a good therapeutic target for the disease.

Keywords: DEFA6, CRC, tumorigenesis

DOI: 10.3233/CBM-182221

Journal: Cancer Biomarkers, vol. 24, no. 4, pp. 485-495, 2019