Wen-Jie Chen1, Ting-Qing Gan2, Hui Qin1, Su-Ning Huang3, Li-Hua Yang2, Ye-Ying Fang3, Zu-Yun Li4, Lin-Jiang Pan5, Gang Chen1. 1. Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China. 2. Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China. 3. Department of Radiology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China. 4. 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. 5. 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.
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.
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: Xuemei Ji; Yohan Bossé; Maria Teresa Landi; Jiang Gui; Xiangjun Xiao; David Qian; Philippe Joubert; Maxime Lamontagne; Yafang Li; Ivan Gorlov; Mariella de Biasi; Younghun Han; Olga Gorlova; Rayjean J Hung; Xifeng Wu; James McKay; Xuchen Zong; Robert Carreras-Torres; David C Christiani; Neil Caporaso; Mattias Johansson; Geoffrey Liu; Stig E Bojesen; Loic Le Marchand; Demetrios Albanes; Heike Bickeböller; Melinda C Aldrich; William S Bush; Adonina Tardon; Gad Rennert; Chu Chen; M Dawn Teare; John K Field; Lambertus A Kiemeney; Philip Lazarus; Aage Haugen; Stephen Lam; Matthew B Schabath; Angeline S Andrew; Hongbing Shen; Yun-Chul Hong; Jian-Min Yuan; Pier A Bertazzi; Angela C Pesatori; Yuanqing Ye; Nancy Diao; Li Su; Ruyang Zhang; Yonathan Brhane; Natasha Leighl; Jakob S Johansen; Anders Mellemgaard; Walid Saliba; Christopher Haiman; Lynne Wilkens; Ana Fernandez-Somoano; Guillermo Fernandez-Tardon; Erik H F M van der Heijden; Jin Hee Kim; Juncheng Dai; Zhibin Hu; Michael P A Davies; Michael W Marcus; Hans Brunnström; Jonas Manjer; Olle Melander; David C Muller; Kim Overvad; Antonia Trichopoulou; Rosario Tumino; Jennifer Doherty; Gary E Goodman; Angela Cox; Fiona Taylor; Penella Woll; Irene Brüske; Judith Manz; Thomas Muley; Angela Risch; Albert Rosenberger; Kjell Grankvist; Mikael Johansson; Frances Shepherd; Ming-Sound Tsao; Susanne M Arnold; Eric B Haura; Ciprian Bolca; Ivana Holcatova; Vladimir Janout; Milica Kontic; Jolanta Lissowska; Anush Mukeria; Simona Ognjanovic; Tadeusz M Orlowski; Ghislaine Scelo; Beata Swiatkowska; David Zaridze; Per Bakke; Vidar Skaug; Shanbeh Zienolddiny; Eric J Duell; Lesley M Butler; Woon-Puay Koh; Yu-Tang Gao; Richard Houlston; John McLaughlin; Victoria Stevens; David C Nickle; Ma'en Obeidat; Wim Timens; Bin Zhu; Lei Song; María Soler Artigas; Martin D Tobin; Louise V Wain; Fangyi Gu; Jinyoung Byun; Ahsan Kamal; Dakai Zhu; Rachel F Tyndale; Wei-Qi Wei; Stephen Chanock; Paul Brennan; Christopher I Amos Journal: Nat Commun Date: 2018-08-13 Impact factor: 14.919