title: HLF/miR-132/TTK axis regulates cell proliferation, metastasis and radiosensitivity of glioma cells.
abstract: Glioma is a malignant cancer with high mortality. A key prognostic factor of glioma is radiosensitivity. It has also been known that microRNAs (miR) significantly contribute to the development of glioma. miR-132 has been previously reported to inhibit tumor growth in some cancers, but not well studied in glioma. It is necessary to understand the association between miR-132 and glioma, including miR-132 expression in glioma, effects of miR-132 on cancer metastasis and radiosensitivity, and the involved molecular mechanism. We first explored the expression levels of miR-132 in human normal and glioma tissues, then correlated the expression levels with different stages of glioma. Utilizing human glioma U87 cells, lentiviral transduction technique, luciferase reporter assay, wound healing assay, transwell invasion assay and clonogenic assay, we investigated the effects of hepatic leukemia factor (HLF), miR-132 and TTK protein kinase (TTK) on cancer cell viability, proliferation, migration, invasion and radiosensitivity. The expression of miR-132 was low in human glioma tissues, and the downregulated expression was associated with advanced glioma grades. HLF directly bound to the BS1 site of miR-132 promoter to enhance the expression of miR-132. HLF-mediated miR-132 was able to directly target and inhibit a downstream factor TTK, which had an oncogenic role. Overexpression of TTK could reverse the inhibitory effects of either miR-132 or HLF on cancer cell proliferation, metastasis and radioresistance. TTK acts as an oncogene in glioma. HLF-mediated miR-132 directly suppresses TTK expression, thus exerting inhibitory effects on cancer cell proliferation, metastasis and radioresistance.
authors: Shanghai Gamma Hospital, 518 Wuzhong Rd (E), Shanghai 200235, China.
authors: Shu
authors: S
authors: Chen
authors: Shanghai Gamma Hospital, 518 Wuzhong Rd (E), Shanghai 200235, China.
authors: Yang
authors: Y
authors: Wang
authors: Shanghai Gamma Hospital, 518 Wuzhong Rd (E), Shanghai 200235, China.
authors: Chunxia
authors: C
authors: Ni
authors: Shanghai Gamma Hospital, 518 Wuzhong Rd (E), Shanghai 200235, China.
authors: Ge
authors: G
authors: Meng
authors: Shanghai Gamma Hospital, 518 Wuzhong Rd (E), Shanghai 200235, China. Electronic address: sheng_xiaofang@sohu.com.
authors: Xiaofang
authors: X
authors: Sheng
mesh_terms: D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011836:Radiation Tolerance / Q000235:genetics; D015398:Signal Transduction
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D018797:Cell Cycle Proteins; C490671:HLF protein, human; C547077:MIRN132 microRNA, human; D035683:MicroRNAs; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C075840:TTK protein, human
keywords: Glioma; HLF; Metastasis; Radiosensitivity; TTK; miR-132