The novel DNA methylation marker FIBIN suppresses non-small cell lung cancer metastasis by negatively regulating ANXA2
作者全名：Peng, Mingyu; Yang, Li; Liao, Jiaxin; Le, Xin; Dai, Fengsheng; Sun, Ran; Wu, Fan; Jiang, Yu; Tian, Rui; Shao, Bianfei; Zhou, Li; Wu, Mingjun; Guo, Shuliang; Xiang, Tingxiu
作者地址：[Peng, Mingyu; Yang, Li; Liao, Jiaxin; Le, Xin; Dai, Fengsheng; Wu, Fan; Jiang, Yu; Guo, Shuliang; Xiang, Tingxiu] Chongqing Med Univ, Affiliated Hosp 1, Dept Resp & Crit Care Med, Chongqing 400016, Peoples R China; [Sun, Ran] Jiulongpo Peoples Hosp, Dept Oncol, Chongqing 400050, Peoples R China; [Wu, Mingjun] Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China; [Peng, Mingyu; Tian, Rui; Shao, Bianfei; Zhou, Li; Xiang, Tingxiu] Chongqing Univ, Canc Hosp, Chongqing Key Lab Translat Res Canc Metastasis &, Chongqing 400030, Peoples R China
通信作者：Guo, SL; Xiang, TX (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Resp & Crit Care Med, Chongqing 400016, Peoples R China.; Wu, MJ (通讯作者)，Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China.
来源：CELLULAR SIGNALLING
ESI学科分类：MOLECULAR BIOLOGY & GENETICS
WOS号：WOS:001239347800001
JCR分区：Q2
影响因子：4.4
年份：2024
卷号：120
期号：
开始页：
结束页：
文献类型：Article
关键词：FIBIN; ANXA2; Metastasis; DNA methylation; Lung cancer
摘要：Objectives: The clinical T1 stage solid lung cancer with metastasis is a serious threat to human life and health. In this study, we performed RNA sequencing on T1 advanced-stage lung cancer and adjacent tissues to identify a novel biomarker and explore its roles in lung cancer. Methods: Quantitative reversed-transcription PCR, reverse transcription PCR and Western blot, MSP and Methtarget were utilized to evaluate FIBIN expression levels at both the transcriptional and protein levels as well as its methylation status. Differential target protein was evaluated for relative and absolute quantitation by isobaric tags. Co -IP was performed to detect the interactions between target protein. Precise location and expression levels of target proteins were revealed by immunofluorescence staining and component protein extraction using specific kits, respectively. Results: We reported that FIBIN was frequently silenced due to promoter hypermethylation in lung cancer. Additionally, both in vitro and in vivo experiments confirmed the significant anti-proliferation and anti-metastasis capabilities of FIBIN. Mechanistically, FIBIN decreased the nuclear accumulation of I3-catenin by reducing the binding activity of GSK3I3 with ANXA2 while promoting interaction between GSK3I3 and I3-catenin. Conclusion: Our findings firstly identify FIBIN is a tumor suppressor, frequently silenced due to promoter hypermethylation. FIBIN may serve as a predictive biomarker for progression or metastasis among early-stage lung cancer patients.
基金机构：Health Joint Medical Research Project [2024QNXM006]; Graduated Research Innovation Project Foundation of Chongqing [CYB22196]
基金资助正文：This work was supported by the National Natural Science Foundation of China (Approval No. 82172619 and No. 82203181), the Chongqing Natural Science Foundation of China (Approval No. CSTC2021jscx-gksb-N0023), the Pharmaceutical and Industrial Integration Project (Approval No. 2022CDJYGRH-002), Key R & D program of Sichuan-Chongqing of the Chongqing Science and Technology Commission (Approval No. CSTB2022TIAD-CUX0001), Chongqing Science andHealth Joint Medical Research Project (Approval No. 2024QNXM006) and Graduated Research Innovation Project Foundation of Chongqing (Approval No. CYB22196) .r Health Joint Medical Research Project (Approval No. 2024QNXM006) and Graduated Research Innovation Project Foundation of Chongqing (Approval No. CYB22196) .
