title: MicroRNA-21 (miR-21) regulates cellular proliferation, invasion, migration, and apoptosis by targeting PTEN, RECK and Bcl-2 in lung squamous carcinoma, Gejiu City, China.
abstract: BACKGROUND
  In South China (Gejiu City, Yunnan Province), lung cancer incidence and associated mortality rate is the most prevalent and observed forms of cancer. Lung cancer in this area is called Gejiu squamous cell lung carcinoma (GSQCLC). Research has demonstrated that overexpression of miR-21 occurs in many cancers. However, the unique relationship between miR-21 and its target genes in GSQCLC has never been investigated. The molecular mechanism involved in GSQCLC must be compared to other non-small cell lung cancers in order to establish a relation and identify potential therapeutic targets.
  
  
  RESULTS
  In the current study, we initially found overexpression of miR-21 occurring in non-small cell lung cancer (NSCLC) cell lines when compared to the immortalized lung epithelial cell line BEAS-2B. We also demonstrated that high expression of miR-21 could increase tumor cell proliferation, invasion, viability, and migration in GSQCLC cell line (YTMLC-90) and NSCLC cell line (NCI-H157). Additionally, our results revealed that miR-21 could suppress YTMLC-90 and NCI-H157 cell apoptosis through arresting cell-cycle at G2/M phase. Furthermore, we demonstrated that PTEN, RECK and Bcl-2 are common target genes of miR-21 in NSCLC. Finally, our studies showed that down-regulation of miR-21 could lead to a significant increase in PTEN and RECK and decrease in Bcl-2 at the mRNA and protein level in YTMLC-90 and NCI-H157 cell lines. However, we have not observed any remarkable difference in the levels of miR-21 and its targets in YTMLC-90 cells when compared with NCI-H157 cells.
  
  
  CONCLUSIONS
  miR-21 simultaneously regulates multiple programs that enhance cell proliferation, apoptosis and tumor invasiveness by targeting PTEN, RECK and Bcl-2 in GSQCLC. Our results demonstrated that miR-21 may play a vital role in tumorigenesis and progression of lung squamous cell carcinoma and suppression of miR-21 may be a novel approach for the treatment of lung squamous cell carcinoma.
authors.affiliation: Key Laboratory for Animal Genetic Diversity and Evolution of High Education in Yunnan Province, Yunnan University, Kunming, Yunnan, China.
authors.forename: Long-Feng
authors.initials: LF
authors.lastname: Xu
authors.affiliation: Tumor Institute, the 3rd Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Wu
authors.affiliation: Tumor Institute, the 3rd Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory for Animal Genetic Diversity and Evolution of High Education in Yunnan Province, Yunnan University, Kunming, Yunnan, China.
authors.forename: Qi-Shun
authors.initials: QS
authors.lastname: Zhu
authors.affiliation: Northeast Missouri Health Co, Kirksville, Missouri, United States of America.
authors.forename: Shoeleh
authors.initials: S
authors.lastname: Hamidi
authors.affiliation: University Health Network, Ontario Cancer Institute and Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada.
authors.forename: Roya
authors.initials: R
authors.lastname: Navab
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D002681:China; D058851:GPI-Linked Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014945:Wound Healing / Q000235:genetics / Q000502:physiology
chemical_list: D058851:GPI-Linked Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; C115460:RECK protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
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