FLOT2 promotes nasopharyngeal carcinoma progression through suppression of TGF-β pathway via facilitating CD109 expression
Hongjuan Xu,
Yuze Yin,
Yihan Li,
Ning Shi,
Wen Xie,
Weiren Luo,
Lei Wang,
Bin Zhu,
Weidong Liu,
Xingjun Jiang,
Caiping Ren
Affiliations
Hongjuan Xu
NHC Key Laboratory of Carcinogenesis, NHC Key Laboratory of Nanobiological Technology, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China; Nuclear Medicine (PET Center), Xiangya Hospital, Central South University, Changsha, Hunan, China
Yuze Yin
NHC Key Laboratory of Carcinogenesis, NHC Key Laboratory of Nanobiological Technology, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, China
Yihan Li
NHC Key Laboratory of Carcinogenesis, NHC Key Laboratory of Nanobiological Technology, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, China
Ning Shi
NHC Key Laboratory of Carcinogenesis, NHC Key Laboratory of Nanobiological Technology, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, China
Wen Xie
NHC Key Laboratory of Carcinogenesis, NHC Key Laboratory of Nanobiological Technology, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, China
Weiren Luo
Cancer Research Institute, Shenzhen Third People’s Hospital, the Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China
Lei Wang
NHC Key Laboratory of Carcinogenesis, NHC Key Laboratory of Nanobiological Technology, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, China
Bin Zhu
NHC Key Laboratory of Carcinogenesis, NHC Key Laboratory of Nanobiological Technology, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, China
Weidong Liu
NHC Key Laboratory of Carcinogenesis, NHC Key Laboratory of Nanobiological Technology, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, China
Xingjun Jiang
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China; Corresponding author
Caiping Ren
NHC Key Laboratory of Carcinogenesis, NHC Key Laboratory of Nanobiological Technology, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, Hunan, China; Corresponding author
Summary: In nasopharyngeal carcinoma (NPC), the TGF-β/Smad pathway genes are altered with inactive TGF-β signal, but the mechanisms remain unclear. RNA-sequencing results showed that FLOT2 negatively regulated the TGF-β signaling pathway via up-regulating CD109 expression. qRT-PCR, western blot, ChIP, and dual-luciferase assays were used to identify whether STAT3 is the activating transcription factor of CD109. Co-IP immunofluorescence staining assays were used to demonstrate the connection between FLOT2 and STAT3. In vitro and in vivo experiments were used to detect whether CD109 could rescue the functional changes of NPC cells resulting from FLOT2 alteration. IHC and Spearman correlation coefficients were used to assay the correlation between FLOT2 and CD109 expression in NPC tissues. Our results found that FLOT2 promotes the development of NPC by inhibiting TGF-β signaling pathway via stimulating the expression of CD109 by stabilizing STAT3, which provides a potential therapeutic strategy for NPC treatment.
