title: Expression of Tim4 in Glioma and its Regulatory Role in LN-18 Glioma Cells.
abstract: BACKGROUND
  Tim4 is a transmembrane protein known as T cell immunoglobulin and mucin domain containing protein-4. We speculated that Tim4 might be associated with glioma. This study aimed to investigate the expression level of Tim4 in gliomas and the regulatory role of Tim4 on the growth and apoptosis of LN-18 glioma cells.
  
  
  METHODS
  Tumor tissues and adjacent normal tissues were collected from patients with glioma. The expression level of Tim4 mRNA and protein was determined by RT-PCR and Western blot analyses, respectively to evaluate their association with glioma. Tim4 was overexpressed or silenced by siRNA interference in cultured human glioma cells LN-18. The growth and apoptosis of LN-18 cells was detected by MTT assay and flow cytometry. The colony-forming ability of LN-18 cells was assessed by the colony formation assay. The collection of human tissues was approved by the Research Ethics Committee at the Harbin Medical University Cancer Hospital and performed in strict accordance with international standards. All patients were required to sign the informed consent.
  
  
  RESULTS
  The expression level of Tim4 mRNA and protein in tumor tissues was significantly higher compared with adjacent normal tissues. Antisense miRNA targeting Tim4 inhibited the growth of LN-18 cells, induced their apoptosis, and reduced their clonogenic capacity. In contrast, overexpression of Tim4 promoted the growth of LN-18 cells, inhibited their apoptosis, and enhanced their clonogenic potential.
  
  
  CONCLUSIONS
  The expression level of Tim-4 is closely associated with glioma. Decreased expression of Tim4 inhibited the growth and colony-forming ability of LN-18 cells and induced their apoptosis, whereas increased expression of Tim4 stimulated the growth and clonogenic potential of LN-18 cells and suppressed their apoptosis.
authors.affiliation: Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan, Shandong, China (mainland).
authors.forename: Weiguo
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan, Shandong, China (mainland).
authors.forename: Xingang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan, Shandong, China (mainland).
authors.forename: Shujun
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan, Shandong, China (mainland).
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Health, Qilu Hospital, Shandong University, Jinan, Shandong, China (mainland).
authors.forename: Qiujie
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D001932:Brain Neoplasms / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C512411:TIMD4 protein, human; C505407:CASP3 protein, human; D053148:Caspase 3