title: Implication of downregulation and prospective pathway signaling of microRNA-375 in lung squamous cell carcinoma.
abstract: BACKGROUND
  Lung cancer is one of the most typical cancers in the world. Altered expression profiles of microRNA-375(miR-375) are linked to many diseases including lung cancer. However, the relationship between miR-375 and lung squamous cell carcinoma (LUSC) is controversial.
  
  
  METHODS
  We first evaluated the 23 LUSCs and the paired normal lung tissues by qRT-PCR. Then we analyzed the LUSC samples with miR-375 expression based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Furthermore, bioinformatics analysis was performed to explore the biological role of miR-375 in LUSC.
  
  
  RESULTS
  The expression of miR-375 was remarkably reduced in LUSC tissues compared with that in paired lung tissues by qRT-PCR (P=0.003). Additionally, the TCGA dataset suggested that miR-375 was significantly downregulated in 478 LUSC tissues compared with 45 normal lung tissues (P<0.0001), as well as the result derived from GEO datasets (the pooled SMD=-1.01; 95%CIs-1.66 to -0.33, P=0.004). Furthermore, a total of 1348 miR-375-related differently expressed genes were identified by the analytical integration, which were involved in critical pathways of LUSC like neuron differentiation, plasma membrane part and sequence-specific DNA binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway examination also unveiled the involvement of target genes in morphine addiction and drug metabolism- other enzymes and neuroactive ligand-receptor interaction. Finally, the expression of WNT5A was inversely correlated with miR-375 expression according to TCGA dataset (r=-0.2342, P<0.0001).
  
  
  CONCLUSIONS
  miR-375 exerts a strong tumor-suppressive effect in LUSC and provided novel insight into the biological function in tumorigenesis and progression of LUSC.
authors.affiliation: Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China.
authors.forename: Ting-Qing
authors.initials: TQ
authors.lastname: Gan
authors.affiliation: Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Qin
authors.affiliation: Department of Radiology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China.
authors.forename: Su-Ning
authors.initials: SN
authors.lastname: Huang
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Yang
authors.affiliation: Department of Radiology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China.
authors.forename: Ye-Ying
authors.initials: YY
authors.lastname: Fang
authors.affiliation: Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China. Electronic address: lizuyun8877@aliyun.com.
authors.forename: Zu-Yun
authors.initials: ZY
authors.lastname: Li
authors.affiliation: Department of Radiology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China. Electronic address: 67666795@qq.com.
authors.forename: Lin-Jiang
authors.initials: LJ
authors.lastname: Pan
authors.affiliation: Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D059467:Transcriptome
chemical_list: C540933:MIRN375 microRNA, human; D035683:MicroRNAs
keywords: Carcinoma; Computational biology; MicroRNAs; Non-small-cell lung