방사선의학 웹진

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Abstract

BACKGROUND:

In humans, sex-determining region-Y (SRY) related high-mobility-group box 4 (SOX4) is linked to development and tumorigenesis. SOX4 is over-expressed in several cancers and has prognostic significance. This study evaluated whether SOX4 affects oncogenic behavior and chemoradiotherapy response in head and neck squamous cell carcinoma (HNSCC) cells, and documented the relationship between its expression and prognosis in oral squamous cell carcinoma (OSCC).

METHODS:

We used small interfering RNA in HNSCC cells to evaluate the effect of SOX4 on cell proliferation, apoptosis, chemoradiation-induced apoptosis, invasion, and migration. SOX4 expression in OSCC tissues was investigated by immunohistochemistry.

RESULTS:

SOX4 knockdown (KO) decreased cell proliferation and induced apoptosis by activating caspases-3 and -7, and poly-ADP ribose polymerase and suppressing X-linked inhibitor of apoptosis protein in HNSCC cells; it also enhanced radiation/cisplatin-induced apoptosis; and suppressed tumor cell invasion and migration. Immunostaining showed SOX4 protein was significantly increased in OSCC tissues compared with adjacent normal mucosa. SOX4 expression was observed in 51.8 % of 85 OSCC tissues, and was significantly correlated with treatment failure (P = 0.032) and shorter overall survival (P = 0.036) in patients with OSCC.

CONCLUSIONS:

SOX4 may contribute to oncogenic phenotypes of HNSCC cells by promoting cell survival and causing chemoradioresistance. It could be a potential prognostic marker for OSCC.
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Author information

Yoon TM1, Kim SA2, Cho WS3, Lee DH4, Lee JK5, Park YL6, Lee KH7, Lee JH8, Kweon SS9, Chung IJ10, Lim SC11, Joo YE12.​

1Departments of Otorhinolaryngology-Head and Neck Surgery, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. yoontm@chonnam.ac.kr.
2Departments of Otorhinolaryngology-Head and Neck Surgery, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. annie0215@naver.com.
3Departments of Otorhinolaryngology-Head and Neck Surgery, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. ggangnet@hanmail.net.
4Departments of Otorhinolaryngology-Head and Neck Surgery, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. lee3l@hanmail.net.
5Departments of Otorhinolaryngology-Head and Neck Surgery, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. joonkyoo@chonnam.ac.kr.
6Departments of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. kokodeak@hanmail.net.
7Departments of Pathology, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. mdkaylee@gmail.com.
8Departments of Pathology, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. jhlee@chonnam.ac.kr.
9Departments of Preventive Medicine, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. ujingogo@paran.com.
10Departments of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. ijchung@chonnam.ac.kr.
11Departments of Otorhinolaryngology-Head and Neck Surgery, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. limsc@chonnama.ac.kr.
12Departments of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, 8 Hak-Dong, Dong-Ku, Gwangju, 501-757, South Korea. yejoo@chonnam.ac.kr.