Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (11): 8-18.doi: 10.6040/j.issn.1671-7554.0.2021.0193

Previous Articles     Next Articles

Prognostic value of POU4F3 in 118 patients with lung adenocarcinoma and its effect on migration of lung adenocarcinoma cells

CHAI Xiaoxue1, YE Hui1, LYU Xinran2, DING Xuchao2, ZHEN Qiulai1, DU Juan3, CAO Lili1,2   

  1. 1. Oncology Department, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250014, Shandong, China;
    2. Oncology Department, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, Shandong, China;
    3. Department of Immunology, Guilin Medical College, Guilin 541004, Guangxi, China
  • Published:2021-11-11

PDF (PC)

161

Abstract: Objective To reveal the expression of POU domain class 4 transcription factor 3(POU4F3)in lung adenocarcinoma(LUAD)tissues and its association with the prognosis of lung adenocarcinoma(LUAD)patients, and to explore the effect of POU4F3 on the migration of LUAD cells. Methods Immunohistochemical staining(IHC)was used to detect the expression of POU4F3 in human LUAD and its adjacent tissues, both of the sample sizes being 118. Log-rank(Mantel-Cox)was used to examine the correlation between POU4F3 expression and the overall survival of LUAD patients. Taking the LUAD cells as the experimental subject, stable overexpression(Lv-POU4F3)and its control(Lv-control)or knockdown of POU4F3(shPOU4F3)and its control(control shRNA)lentivirus were constructed and transfected into SPCA1 and A549 cells, respectively. Western blotting was conducted to verify the efficiency of POU4F3 overexpression or knockdown transfection. Cell migration was detected by wound healing, Transwell migration assay, and phalloidine fluorescence experiment. Results IHC analysis showed that the expression of POU4F3 in LUAD tissues was significantly lower than that in adjacent tissues(1.5 vs 4.0), and the difference was statistically significant(P<0.001). Compared with LUAD patients with low POU4F3 expression, patients with high POU4F3 expression had significantly longer overall survival(HR=2.04, 95%CI: 1.158-3.607, P=0.028). Cell experiment results showed that stably transfected LUAD cell lines overexpressing or knocking down POU4F3 were constructed effectively. After overexpression of POU4F3, the wound healing expreriment showed that the wound healing rate of cells in the Lv-POU4F3 group was lower than that in the Lv-control group, the difference was statistically significant(FSPCA1 treatment=69.86, PSPCA1=0.001; FA549 treatment=492.10, PA549<0.001). Transwell migration assay showed that the number of transmembrane cells in the SPCA1-Lv-POU4F3 group was less than that in the SPCA1-Lv-control group(599.0±11.36 vs 806.3±18.72, t=16.40, P<0.001), and the number of transmembrane cells in the A549-Lv-POU4F3 group was less than that in the A549-Lv-control group(181.0±18.68 vs 314.7±23.46, t=7.72, P=0.002). The phalloidine fluorescence experiment showed that SPCA1 cells with overexpression of POU4F3 had thinner microfillets and fewer pseudopodia. The mean fluorescence intensity of Lv-POU4F3 group was lower than that of Lv-control group(23.30±1.34 vs 33.45±1.85), and the difference was statistically significant(t=7.67, P=0.002). After POU4F3 was knocked down, wound healing experiment showed that the cell wound healing rate of shPOU4F3 group was higher than that of control shRNA group, the difference was statistically significant(FSPCA1 treatment=114.60, PSPCA1<0.001; FA549 treatment=1 710.00, PA549<0.001). Transwell migration assay showed that the number of transmembrane cells in SPCA1-shPOU4F3 group was higher than that in the SPCA1-control shRNA group(970.00±14.53 vs 585.00±25.53, t=22.70, P<0.001), and the number of transmembrane cells in A549-shPOU4F3 group was higher than that in the A549-control shRNA group(528.00±29.14 vs 185.30±9.50, t=19.37, P<0.001). The phalloidine fluorescence experiment showed that after knockdown of POU4F3, SPCA1 cell microfilules became thicker and pseudopodia increased. The mean fluorescence intensity of shPOU4F3 group was higher than that of control shRNA group(48.53±3.30 vs 31.07±2.32), and the difference was statistically significant(t=7.50, P=0.002). Conclusion The expression of POU4F3 in human LUAD tissues is significantly lower than that in para-cancerous tissues. LUAD patients with high expression of POU4F3 have a better prognosis. POU4F3 can inhibit the migration of LUAD cells. POU4F3 may be a novel tumor suppressor gene of LUAD and a new target for the diagnosis and treatment of LUAD.

Key words: Lung adenocarcinoma, POU domain class 4 transcription factor 3, Overall survival, Migration

CLC Number: 

  • R734.2
[1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(1): 7-30.
[2] Chen W, Zheng R, Baade PD, et al. Cancer statistics in china, 2015 [J]. CA Cancer J Clin, 2016, 66(2): 115-132.
[3] Singh D, Attri BK, Gill RK, et al. Review on EGFR inhibitors: critical updates [J]. Mini Rev Med Chem, 2016, 16(14): 1134-1166.
[4] Tsao MS, Sakurada A, Cutz JC, et al. Erlotinib in lung cancer-molecular and clinical predictors of outcome [J]. N Engl J Med, 2005, 353(2): 133-144.
[5] Barreca A, Lasorsa E, Riera L, et al. Anaplastic lymphoma kinase in human cancer [J]. J Mol Endocrinol, 2011, 47(1): R11-R23.
[6] Bhatnagar V, Gormley NJ, Luo L, et al. Fda approval summary: daratumumab for treatment of multiple myeloma after one prior therapy [J]. Oncologist, 2017, 22(11): 1347-1353.
[7] Kasamon YL, de Claro RA, Wang Y, et al. FDA approval summary: nivolumab for the treatment of relapsed or progressive classical Hodgkin lymphoma [J]. Oncologist, 2017, 22(5): 585-591.
[8] Fashoyin-Aje L, Donoghue M, Chen H, et al. FDA approval summary: pembrolizumab for recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma expressing PD-L1 [J]. Oncologist, 2019, 24(1): 103-109.
[9] Kazandjian D, Suzman DL, Blumenthal G, et al. FDA approval summary: nivolumab for the treatment of metastatic non-small cell lung cancer with progression on or after platinum-based chemotherapy [J]. Oncologist, 2016, 21(5): 634-642.
[10] Herr W, Sturm RA, Clerc RG, et al. The POU domain: a large conserved region in the mammalian pit-1, oct-1, oct-2, and Caenorhabditis elegans unc-86 gene products [J]. Genes Dev, 1988, 2(12A): 1513-1516.
[11] Vahava O, Morell R, Lynch ED, et al. Mutation in transcription factor POU4F3 associated with inherited progressive hearing loss in humans [J]. Science, 1998, 279(5358): 1950-1954.
[12] Weiss S, Gottfried I, Mayrose I, et al. The DFNA15 deafness mutation affects POU4F3 protein stability, localization, and transcriptional activity [J]. Mol Cell Biol, 2003, 23(22): 7957-7964.
[13] Masuda M, Li Y, Pak K, et al. The promoter and multiple enhancers of the POU4F3 gene regulate expression in inner ear hair cells [J]. Mol Neurobiol, 2017, 54(7): 5414-5426.
[14] He L, Pang X, Chen P, et al. Mutation in the hair cell specific gene POU4F3 is a common cause for autosomal dominant nonsyndromic hearing loss in Chinese Hans [J]. Neural Plast, 2016, 2016: 9890827. doi: 10.1155/2016/9890827.
[15] Freitas ÉL, Oiticica J, Silva AG, et al. Deletion of the entire POU4F3 gene in a familial case of autosomal dominant non-syndromic hearing loss [J]. Eur J Med Genet, 2014, 57(4): 125-128.
[16] Sayyad Z, Sirohi K, Radha V, et al. 661W is a retinal ganglion precursor-like cell line in which glaucoma-associated optineurin mutants induce cell death selectively [J]. Sci Rep, 2017, 7(1): 16855.
[17] Leonard JH, Cook AL, Van Gele M, et al. Proneural and proneuroendocrine transcription factor expression in cutaneous mechanoreceptor(Merkel)cells and Merkel cell carcinoma [J]. Int J Cancer, 2002, 101(2): 103-110.
[18] Chen YC, Huang RL, Huang YK, et al. Methylomics analysis identifies epigenetically silenced genes and implies an activation of β-catenin signaling in cervical cancer [J]. Int J Cancer, 2014, 135(1): 117-127.
[19] Kocsis A, Takács T, Jeney C, et al. Performance of a new HPV and biomarker assay in the management of hrHPV positive women: subanalysis of the ongoing multicenter TRACE clinical trial(n>6,000)to evaluate POU4F3 methylation as a potential biomarker of cervical precancer and cancer [J]. Int J Cancer, 2017, 140(5): 1119-1133.
[20] Wu X, Rauch TA, Zhong X, et al. CpG island hypermethylation in human astrocytomas [J]. Cancer Res, 2010, 70(7): 2718-2727.
[21] 周春燕,药立波.生物化学与分子生物学[M].9版.北京:人民卫生出版社,2018: 405.
[22] Morris LG, Chan TA. Therapeutic targeting of tumor suppressor genes [J]. Cancer, 2015, 121(9): 1357-1368.
[23] Klein CA. Parallel progression of primary tumours and metastases [J]. Nat Rev Cancer, 2009, 9(4): 302-312.
[24] 丁兰,柳志军,令利军,等.虎刺醛对人肝癌细胞HepG2生长抑制、细胞迁移抑制及其机制的研究[J].中国细胞生物学学报, 2013, 35(4): 442-449. DING Lan, LIU Zhijun, LING Lijun, et al. Study of damnacanthal on anti-proliferation, cell migration inhibition and its mechanism in human hepatoma cell HepG2 [J]. Chinese Journal of Cell Biology, 2013, 35(4): 442-449.
[25] 黄蕾,滕春莹,雷鹏,等.伪足、有氧糖酵解与肿瘤细胞迁移的研究进展[J].癌变·畸变·突变, 2020, 32(1): 72-75.
[26] Chazotte B. Labeling cytoskeletal F-actin with rhodamine phalloidin or fluorescein phalloidin for imaging [J]. Cold Spring Harb Protoc, 2010, 2010(5): pdb.prot4947. doi: 10.1101/pdb.prot4947.
[1] ZHANG Zhenwei, LI Jia, CHEN Keming. IGF2BP2/m6A/ITGA5 signal axis regulates the proliferation and migration of renal clear cells [J]. Journal of Shandong University (Health Sciences), 2022, 60(9): 74-84.
[2] CHEN Zhaobo, FANG Min, XUE Haoran, LIU Chunyan. Deubiquitinase USP35 promotes the cells migration and invasion of non-small cell lung cancer [J]. Journal of Shandong University (Health Sciences), 2022, 60(4): 30-37.
[3] ZHENG Haotian, WANG Guanghui, ZHAO Xiaogang, WANG Yadong, ZENG Yukai, DU Jiajun. A prognostic risk model for LKB1 mutant lung adenocarcinoma based on aberrant DNA methylation sites [J]. Journal of Shandong University (Health Sciences), 2022, 60(3): 51-58.
[4] SUN Qingjie, ZHANG Yisha, GUAN Shanghui, FENG Zhihui. Effects of valproic acid on the survival and tumor recurrence of 134 patients with glioma treated with radiotherapy [J]. Journal of Shandong University (Health Sciences), 2021, 59(8): 80-85.
[5] KONG Xue, LI Juan, DUAN Weili, SHI Shuang, LI Peilong, DU Lutao, MAO Haiting, WANG Chuanxin. Effects of lncRNA AC012073.1 on the migration and invasion of human breast cancer cells and its clinical significance [J]. Journal of Shandong University (Health Sciences), 2021, 59(4): 70-78.
[6] XUE Yuan, LIN Xueyan, XU Ge, TIAN Yongjie. Expression of hypoxia-inducible factor-1α in the serum of patients with endometriosis and its effect on epithelial mesenchymal transition of eutopic endometrial stromal cells [J]. Journal of Shandong University (Health Sciences), 2021, 59(2): 41-47.
[7] YANG Jia, ZHANG Man, CHEN Kaiming, CAO Xi. Mechanism of miR-146a accelerating macrophage migration induced arteriosclerosis via TLR4/MyD88 pathway [J]. Journal of Shandong University (Health Sciences), 2021, 59(11): 1-7.
[8] PANG Zhaofei, LIU Yong, ZHAO Xiaogang, YAN Tao, CHEN Xiaowei, DU Jiajun. Construction of a stemness-based scoring model predicting the efficacy of immunotherapy in lung adenocarcinoma based on public databases [J]. Journal of Shandong University (Health Sciences), 2021, 59(11): 19-28.
[9] SUN Yifeng, GAO Yu, LIANG Yongyuan, GAO Yang. Expression of CPLX2 and its in vitro effects on the proliferation migration and invasion of hepatocellular carcinoma cells [J]. Journal of Shandong University (Health Sciences), 2020, 1(9): 34-39.
[10] LI Ning, LI Juan, XIE Yan, LI Peilong, WANG Yunshan, DU Lutao, WANG Chuanxin. Expression of LncRNA AL109955.1 in 80 cases of colorectal cancer and its effect on cell proliferation, migration and invasion [J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 38-46.
[11] MA Qingyuan, PU Peidong, HAN Fei, WANG Chao, ZHU Zhoujun, WANG Weishan, SHI Chenhui. Effect of miR-27b-3p regulating SMAD1 on osteosarcoma cell proliferation, migration and invasion [J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 32-37.
[12] YANG Xiuting, LIU Qigong, ZUO Ping, LIU Zhengxiang, ZUO Houjuan. Effect of CD151-MUT mutation on migration of lung adenocarcinoma cell line A549 and its mechanism [J]. Journal of Shandong University (Health Sciences), 2020, 58(3): 81-86.
[13] SHI Li, MA Jing, ZHAO Xiwa, GUAN Yingxia, ZHAO Lianmei, SHAN Baoen. Expression and function of miR-25-3p in endometrial cancer [J]. Journal of Shandong University (Health Sciences), 2020, 58(12): 86-91.
[14] HONG Jiageng, NIE Yangyang, SU Guoqiang. Effects of propofol on proliferation, migration and expressions of Wnt1 and β-catenin in colon cancer cells [J]. Journal of Shandong University (Health Sciences), 2020, 58(11): 53-58.
[15] LUO Mengying, WU Bei, WANG Ye, LUO Heng, CAO Yu. Effect of ar-turmerone on poliferation, migration and invasion of cervical squamous cancer cell line SiHa [J]. Journal of Shandong University (Health Sciences), 2019, 57(6): 68-74.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] WANG Huan-liang,SUN Bao-zhu,DU Hong-mei,ZHOU Chang-qing,ZHANG Li. Controlling the depth of propofol anesthesia using the bispectral indexand the systolic blood pressure[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2006, 44(5): 471 -474 .
[2] HUANGQing,TIAN Hui,LI Lin,LIANG Fei,LIU Xi-xian. [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2006, 44(6): 556 -559 .
[3] ZHU Mei-jia,HAN Ju,WANG Xin-yi,LU Wei,WANG Ai-hua,GUAN Xin-hua,CAO Xia,CAO Bing-zhen. [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2006, 44(8): 834 -839 .
[4] ZENG Ji-ping,WANG Li-na,WANG Li-xiang,REN Xiao-hui,ZHANG Meng-ye,XIA Wen,CUI Xing. [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2006, 44(5): 467 -470 .
[5] SHU Ya,QI Feng. Jaw thrust device (JTD) on obesity patients for maintaining the airway patency during general anesthesia induction[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(10): 1072 -1074 .
[6] SONG Yong-hong,MA Chun-hong,LV Hong-juan,ZHU Chuan-fu,NIE Xiang-min,WANG Mei,LIU Yan,ZHANG Ping. HLA allele polymorphism in northern Hans of China[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(6): 546 -553 .
[7] SONG Hai-yan, WU Yu-ling, ZHANG Yan-ping. Protective effect of oyster extract on apoptotic cells in neural tube defect induced by hyperthermia[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(2): 113 -116 .
[8] YU Hui1,2, CHEN Shaohua1, ZHAO Jiajun2, GAO Ling3
. Effects of ethanol on glycogen content, GSK3β，
and PAMPK of L02 cells[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(04): 75 -78 .
[9] WANG Zhi-ang,DING Xua,SUN Peng/sup>,WANG Cheng-wei,HAO Xiao-guang,PAN Shun. Role of pre-operative cerebral angiography in cerebral artery stenosis stent angioplasty[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(2): 146 -148 .
[10] HOU Xiao-yang,BU Pei-li,ZHANG Yun,FENG Jin-bo,LIU Chun-xi,LI Chuan-bao,HAO Ming-xiu. Peroxisome proliferatorsactivated receptor α play a critical role in the inhibition of myocardial fibrosis induced by AngⅡ in vitro[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(7): 665 -668 .
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd