A gender specific improved survival related to stromal miR-143 and miR-145 expression in non-small cell lung cancer

被引:0
作者
Kaja Skjefstad
Charles Johannessen
Thea Grindstad
Thomas Kilvaer
Erna-Elise Paulsen
Mona Pedersen
Tom Donnem
Sigve Andersen
Roy Bremnes
Elin Richardsen
Samer Al-Saad
Lill-Tove Busund
机构
[1] UiT The Arctic University of Norway,Department of Medical Biology
[2] UiT The Arctic University of Norway,Department of Clinical Medicine
[3] University Hospital of North Norway,Department of Oncology
[4] University Hospital of North Norway,Department of Clinical Pathology
[5] Mailbox 46,undefined
来源
Scientific Reports | / 8卷
关键词
D O I
暂无
中图分类号
学科分类号
摘要
Micro RNAs (miRNA) are small non-coding RNAs that post-transcriptionally regulate gene expression. Dysregulation of miRNA cluster 143/145 has been reported in several malignancies, but their role in non-small cell lung cancer (NSCLC) remains elusive. This study investigates the prognostic impact of miR-143 and miR-145 in primary tumors and metastatic lymph nodes in NSCLC tissue. Tissue from 553 primary tumors and 143 matched metastatic lymph nodes were collected and tissue microarrays were constructed. In situ hybridization was used to evaluate miR-143 and miR-145 expression in tumor epithelial cells and stromal cells in the primary tumors and lymph nodes. In vivo data was supplemented with functional studies of cell lines in vitro to evaluate the role of miR-143 and miR-145 in NSCLC tumorigenesis. In our cohort, stromal miR-143 (S-miR-143) and miR-145 (S-miR-145) expression in primary tumor tissue were independent prognosticators of improved disease-specific survival (DSS) in female (S-miR-143, HR: 0.53, p = 0.019) and male patients (S-miR-145, HR: 0.58, p = 0.021), respectively. Interesting correlations between the miR cluster 143/145 and previously investigated steroid hormone receptors from the same cohort were identified, substantiating their gender dependent significance.
引用
收藏
相关论文
共 90 条
[1]  
Siegel RL(2016)Cancer statistics, 2016 CA: a cancer journal for clinicians 66 7-30
[2]  
Miller KD(2004)MicroRNAs: genomics, biogenesis, mechanism, and function Cell 116 281-297
[3]  
Jemal A(2004)Specificity of microRNA target selection in translational repression Genes & development 18 504-511
[4]  
Bartel DP(2006)Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34 MicroRNA signatures in human cancers. 6 857-5930
[5]  
Doench JG(2010)Clinical development of TargomiRs, a miRNA mimic-based treatment for patients with recurrent thoracic cancer Cancer research 70 5923-1085
[6]  
Sharp PA(2016)Lessons from miR-143/145: the importance of cell-type localization of miRNAs Epigenomics 8 1079-7538
[7]  
Calin GA(2014)Loss of microRNA-143/145 disturbs cellular growth and apoptosis of human epithelial cancers by impairing the MDM2-p53 feedback loop Nucleic acids research 42 7528-1802
[8]  
Croce CM(2013)miR-145 participates with TP53 in a death-promoting regulatory loop and targets estrogen receptor-α in human breast cancer cells Oncogene 32 61-51
[9]  
Wiggins JF(2010)miR-143 suppresses the proliferation of NSCLC cells by inhibiting the epidermal growth factor receptor Cell death and differentiation 17 246-2428
[10]  
Reid G(2016)miRNA-145 inhibits non-small cell lung cancer cell proliferation by targeting c-Myc Experimental and Therapeutic Medicine 12 1795-391