title: TTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1β/Derlin-1 pathway.
abstract: Circular RNAs are a subgroup of non-coding RNAs and generated by a mammalian genome. Herein, the expression and function of circular RNA circ-TTBK2 were investigated in human glioma cells.
  
  
  
  Fluorescence in situ hybridization and quantitative real-time PCR were conducted to profile the cell distribution and expression of circ-TTBK2 and microRNA-217 (miR-217) in glioma tissues and cells. Immunohistochemical and western blot were used to determine the expression of HNF1β and Derlin-1 in glioma tissues and cells. Stable knockdown of circ-TTBK2 or overexpression of miR-217 glioma cell lines (U87 and U251) were established to explore the function of circ-TTBK2 and miR-217 in glioma cells. Further, luciferase reports and RNA immunoprecipitation were used to investigate the correlation between circ-TTBK2 and miR-217. Cell Counting Kit-8, transwell assays, and flow cytometry were used to investigate circ-TTBK2 and miR-217 function including cell proliferation, migration and invasion, and apoptosis, respectively. ChIP assays were used to ascertain the correlations between HNF1β and Derlin-1.
  
  
  
  We found that circ-TTBK2 was upregulated in glioma tissues and cell lines, while linear TTBK2 was not dysregulated in glioma tissues and cells. Enhanced expression of circ-TTBK2 promoted cell proliferation, migration, and invasion, while inhibited apoptosis. MiR-217 was downregulated in glioma tissues and cell lines. We also found that circ-TTBK2, but not linear TTBK2, acted as miR-217 sponge in a sequence-specific manner. In addition, upregulated circ-TTBK2 decreased miR-217 expression and there was a reciprocal negative feedback between them in an Argonaute2-dependent manner. Moreover, reintroduction of miR-217 significantly reversed circ-TTBK2-mediated promotion of glioma progression. HNF1β was a direct target of miR-217, and played oncogenic role in glioma cells. Remarkably, circ-TTBK2 knockdown combined with miR-217 overexpression led to tumor regression in vivo.
  
  
  
  These results demonstrated a novel role circ-TTBK2 in the glioma progression.
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.|Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang, 110004, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.|Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang, 110004, People's Republic of China.
authors.forename: Xiaobai
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, 110122, People's Republic of China.|Key Laboratory of Cell Biology, Ministry of Public Health of China, and Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang, 110122, People's Republic of China.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, 110122, People's Republic of China.|Key Laboratory of Cell Biology, Ministry of Public Health of China, and Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang, 110122, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, 110122, People's Republic of China.|Key Laboratory of Cell Biology, Ministry of Public Health of China, and Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang, 110122, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.|Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang, 110004, People's Republic of China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Xi
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.|Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang, 110004, People's Republic of China.
authors.forename: Zhongyou
authors.initials: Z
authors.lastname: Que
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China. liuyh_cmuns@163.com.|Liaoning Research Center for Translational Medicine in Nervous System Disease, Shenyang, 110004, People's Republic of China. liuyh_cmuns@163.com.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Liu
mesh_terms: D017209:Apoptosis; D001706:Biopsy; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005910:Glioma / Q000473:pathology*; D051539:Hepatocyte Nuclear Factor 1-beta / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D035683:MicroRNAs / Q000032:analysis / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012313:RNA / Q000032:analysis / Q000502:physiology*; D000079962:RNA, Circular; D015398:Signal Transduction
chemical_list: C487709:DERL1 protein, human; C496495:HNF1B protein, human; C553315:MIRN217 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D000079962:RNA, Circular; D051539:Hepatocyte Nuclear Factor 1-beta; D012313:RNA; C095903:tau-tubulin kinase; D017346:Protein Serine-Threonine Kinases
keywords: Circular RNAs; Glioma; MicroRNAs; circ-TTBK2; miR-217