High expression of RAI14 promotes bone metastasis in prostate cancer and is associated with poor prognosis

doi:10.3969/j.issn.1009-976X.2023.02.006

Abstract

Abstract: Objective To investigate the correlation between the high expression of RAI14 in prostate cancer cell lines and poor prognosis, as well as its promotion and mechanism of bone metastasis in prostate cancer. Methods Screening the differentially expressed genes most closely related to bone metastasis of prostate cancer through bioinformatics analysis of the database； Explore the expression of RAI14 in prostate cancer cell lines through PCR experiments and explore the relationship between RAI14 and disease free survival through statistical analysis； Using transwell migration and invasion experiments and in vitro co culture experiments to explore the impact of RAI14 on the progression of prostate cancer； Preliminary exploration of the downstream signal pathway of RAI14 through bioinformatics analysis and western blot experiments. Results Survival analysis and clinical correlation analysis showed that RAI14 was most closely related to bone metastasis of prostate cancer； RAI14 was highly expressed in prostate cancer cell lines and had a lower disease-free survival rate； In vitro functional experiments and bioinformatics analysis showed that RAI14 can promote bone metastasis of prostate cancer； Through bioinformatics analysis and WB experiments, it was found that RAI14 plays a role by activating the AKT pathway. Conclusion In the present study, RAI14 was highly expressed in prostate cancer promoted the progression of prostate cancer, regulated bone metastasis of prostate cancer by activating AKT signaling pathways, and was related to poor prognosis.

Key words: prostate cancer, bone metastasis, RAI14, AKT

摘要： 目的探究RAI14在前列腺癌细胞系中的高表达与不良预后的相关性及其对前列腺癌骨转移的促进及机制。方法通过对数据库进行生信分析筛选出与前列腺癌骨转移最密切的差异基因; 通过PCR实验探究RAI14在前列腺癌细胞系中的表达情况并通过统计分析探究RAI1 4与无病生存率的关系; 使用transwell迁移和侵袭实验、体外共培养实验探究RAI14对前列腺癌进展的影响; 通过生信分析和western blot实验初步探究RAI14的下游信号通路; 结果生存分析和临床相关性分析筛选发现RAI14与前列腺癌骨转移关系最密切; RAI14在前列腺癌肿瘤细胞系中高表达,并且有着更低的无病生存率; 体外功能学实验及生信分析均表明RAI14能够促进前列腺癌的骨转移; 通过生信分析及WB实验发现RAI14通过激活AKT通路发挥作用。结论 RAI14在前列腺癌中高表达并可能通过激活AKT信号通路进而调控前列腺癌的骨转移; RAI14的高表达可能与前列腺癌不良预后相关。

关键词: 前列腺癌, 骨转移, RAI14, AKT

CLC Number:

R737.25

FAN Hui-yang, LAI Yi-ming, ZHOU Jie, CHEN Yong-ming, TANG Chen, LI Ling-feng, WU Yongxin, GUO Zheng-hui. High expression of RAI14 promotes bone metastasis in prostate cancer and is associated with poor prognosis[J]. Lingnan Modern Clinics In Surgery, 2023, 23(02): 127-134.

范辉阳, 赖义明, 周杰, 陈勇明, 唐晨, 李凌峰, 吴永鑫, 郭正辉. RAI14高表达促进前列腺癌骨转移并与不良预后相关[J]. 岭南现代临床外科, 2023, 23(02): 127-134.

References

[1] Erratum: Global cancerstatistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2020, 70(4):313.
[2] Pradhan AK, Bhoopathi P, Talukdar S, et al.Recombinant MDA-7/IL24 Suppresses Prostate Cancer Bone Metastasis through Downregulation of the Akt/Mcl-1 Pathway[J]. Mol Cancer Ther, 2018, 17(9): 1951-1960.
[3] Kelly SP, Anderson WF, Rosenberg PS, et al.Past, Current, and Future Incidence Rates and Burden of Metastatic Prostate Cancer in the United States[J]. Eur Urol Focus, 2018, 4(1): 121-127.
[4] Zang G, Mu Y, Gao L, et al.PKCζ facilitates lymphatic metastatic spread of prostate cancer cells in a mice xenograft model[J]. Oncogene, 2019, 38(22): 4215-4231.
[5] Löppenberg B, Dalela D, Karabon P et al. The Impact of Local Treatment on Overall Survival in Patients with Metastatic Prostate Cancer on Diagnosis: A National Cancer Data Base Analysis[J]. Eur Urol, 2017, 72(1): 14-19.
[6] Ziu E, Mesfin FB. Cancer, Metastasis, Spinal [EB/OL]. Treasure Island (FL): StatPearls Publishing; 2018.
[7] Shorning BY, Dass MS, Smalley MJ, et al.The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling[J]. Int J Mol Sci, 2020, 21(12): 4507.
[8] Peng YF, Mandai K, Sakisaka T, et al.Ankycorbin: a novel actin cytoskeleton-associated protein[J]. Genes Cells, 2000, 5(12): 1001-1008.
[9] Zhou J,Yong WP, Yap CS, et al.An Integrative Approach Identified Genes Associated with Drug Response in Gastric Cancer[J]. Carcinogenesis. 2015; 36(4): 441-451.
[10] He XY, Zhao J, Chen ZQ, et al.High Expression of Retinoic Acid Induced 14 (RAI14) in Gastric Cancer and Its Prognostic Value[J]. Med Sci Monit, 2018, 24:2244-2251.
[11] Chen C,Maimaiti A, Zhang X, et al.Knockdown of RAI14 Suppresses the Progression of Gastric Cancer[J]. Onco Targets Ther, 2018, 11: 6693-6703.
[12] Yuan C, Hu H, Kuang M, et al.Super enhancer associated RAI14 is a new potential biomarker in lung adenocarcinoma[J]. Oncotarget, 2017, 8(62): 105251-105261.
[13] Hawkins SM, Loomans HA, Wan YW, et al.Expression and functional pathway analysis of nuclear receptor NR2F2 in ovarian cancer[J]. J Clin Endocrinol Metab, 2013, 98(7): E1152-1162.
[14] Paez AV, Pallavicini C, Schuster F, et al.Heme oxygenase-1 in the forefront of a multi-molecular network that governs cell-cell contacts and filopodia-induced zippering in prostate cancer[J]. Cell Death Dis, 2016, 7(12): e2570.
[15] Su F, He W, Chen C, et al.The long non-coding RNA FOXD2-AS1 promotes bladder cancer progression and recurrence through a positive feedback loop with Akt and E2F1[J]. Cell Death Dis, 2018, 9(2): 233.
[16] Blattner M, Liu D, Robinson BD, et al.SPOP Mutation Drives Prostate Tumorigenesis In Vivo through Coordinate Regulation of PI3K/mTOR and AR Signaling[J]. Cancer Cell, 2017, 31(3): 436-451.
[17] Chen C, Cai Q, He W, et al.AP4 modulated by the PI3K/AKT pathway promotes prostate cancer proliferation and metastasis of prostate cancer via upregulating L-plastin[J]. Cell Death Dis, 2017, 8(10): e3060.
[18] Millis SZ, Jardim DL, Albacker L, et al.Phosphatidylinositol 3-kinase pathway genomic alterations in 60,991 diverse solid tumors informs targeted therapy opportunities[J]. Cancer, 2019, 125(7): 1185-1199.
[19] Taylor BS, Schultz N, Hieronymus H, et al.Integrative genomic profiling of human prostate cancer[J]. Cancer Cell, 2010, 18(1): 11-22.