title: The ratio of FoxA1 to FoxA2 in lung adenocarcinoma is regulated by LncRNA HOTAIR and chromatin remodeling factor LSH.
abstract: The lncRNA HOTAIR is a critical regulator of cancer progression. Chromatin remodeling factor LSH is critical for normal development of plants and mammals. However, the underlying mechanisms causing this in cancer are not entirely clear. The functional diversification of the FOXA1 and FOXA2 contributes to the target genes during evolution and carcinogenesis. Little is known about the ratio of FOXA1 to FOXA2 in cancer. We here found that both HOTAIR and LSH overexpression was significantly correlated with poor survival in patients with lung adenocarcinoma cancer (ADC). Also, the ratio of FOXA1 and FOXA2 is linked with poor survival in patients with lung ADC. HOTAIR regulates the ratio of FOXA1 to FOXA2 and migration and invasion. HOTAIR and the ratio of FOXA1 to FOXA2 are negatively correlated. HOTAIR knockdown inhibits migration and invasion. HOTAIR is associated with LSH, and this association linked with the binding of LSH in the promoter of FOXA1, not FOXA2. Targeted inhibition of HOTAIR suppresses the migratory and invasive properties. These data suggest that HOTAIR is an important mediator of the ratio of FOXA1 and FOXA2 and LSH involves in, and suggest that HOTAIR inhibition may represent a promising therapeutic option for suppressing lung ADC progression.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Second Xiangya Hospital of Central South University, Changsha, China.
authors.forename: Ranran
authors.initials: R
authors.lastname: Wang
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan, 410078 China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, 410078 China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, 410078 China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan, 410078 China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, 410078 China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, 410078 China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan, 410078 China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, 410078 China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, 410078 China.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan, 410078 China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, 410078 China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, 410078 China.
authors.forename: Chao
authors.initials: C
authors.lastname: Mao
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan, 410078 China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, 410078 China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, 410078 China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yan
authors.affiliation: Center for Medicine Research, Xiangya Hospital, Central South University, Changsha, Hunan, 410078 China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.affiliation: College of Medical Sciences, Washington State University Spokane, 412 E. Spokane Falls Boulevard, Spokane, WA 99202, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Shan
authors.affiliation: Cancer Research Institute, Central South University, Changsha, Hunan, 410078 China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, 410078 China.|Key Laboratory of Carcinogenesis, Ministry of Health, Hunan, 410078 China.
authors.forename: Yongguang
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Second Xiangya Hospital of Central South University, Changsha, China.|Cancer Research Institute, Central South University, Changsha, Hunan, 410078 China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000235:genetics*; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011485:Protein Binding; D062085:RNA, Long Noncoding / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C496499:FOXA1 protein, human; C496502:FOXA2 protein, human; C561566:HOTAIR long untranslated RNA, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D062085:RNA, Long Noncoding; D051542:Hepatocyte Nuclear Factor 3-beta; D004265:DNA Helicases; C412063:HELLS protein, human