Long non-coding RNA ATB promotes glioma malignancy by negatively regulating miR-200a.
Glioma is one of the most common and aggressive primary malignant tumor in the brain. Accumulating evidences indicated that aberrantly expressed non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), contribute to tumorigenesis. However, potential mechanisms between lncRNAs and miRNAs in glioma remain largely unknown.



Long non-coding RNA activated by TGF-β (LncRNA-ATB) expression in glioma tissues and cells was quantified by quantitative reverse transcription-PCR. Glioma cell lines U251 and A172 were transfected with sh-ATB, miR-200a mimics, miR-200a inhibitors, after we assayed the cell phenotype and expression of the relevant molecules. Dual-luciferase reporter assay, RIP and a xenograft mouse model were used to examine the expression of sh-ATB and its target gene miR-200a.



ATB is abnormally up-regulated both in glioma tissues and cell lines compared with normal brain tissues, and glioma patients with high ATB expression had shorter overall survival time. Knockdown of ATB significantly inhibits glioma malignancy, including cell proliferation, colony formation, migration, invasion in vitro, and the xenograft tumor formation in vivo. In addition, ATB was confirmed to target miR-200a, and miR-200a inhibition reversed the malignant characteristics of ATB knockdown on glioma cells. In particular, ATB may act as a ceRNA, effectively becoming a sink for miR-200a, thereby modulating the derepression of TGF-β2.



Our findings suggest that ATB plays an oncogenic role of glioma cells by inhibiting miR-200a and facilitating TGF-β2 in glioma, thereby may represent a potential therapeutic target for the treatment of human glioma.
Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 678 Fu Rong Road, Hefei, Anhui Province, China, 230601.|Cerebral Vascular Disease Research Center, Anhui Medical University, 678 Fu Rong Road, Hefei, Anhui Province, China, 230601.
Chun-Chun
CC
Ma
Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 678 Fu Rong Road, Hefei, Anhui Province, China, 230601.|Cerebral Vascular Disease Research Center, Anhui Medical University, 678 Fu Rong Road, Hefei, Anhui Province, China, 230601.
Zhang
Z
Xiong
Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 678 Fu Rong Road, Hefei, Anhui Province, China, 230601.|Cerebral Vascular Disease Research Center, Anhui Medical University, 678 Fu Rong Road, Hefei, Anhui Province, China, 230601.
Guan-Nan
GN
Zhu
Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 678 Fu Rong Road, Hefei, Anhui Province, China, 230601.|Cerebral Vascular Disease Research Center, Anhui Medical University, 678 Fu Rong Road, Hefei, Anhui Province, China, 230601.
Chao
C
Wang
Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 678 Fu Rong Road, Hefei, Anhui Province, China, 230601.|Cerebral Vascular Disease Research Center, Anhui Medical University, 678 Fu Rong Road, Hefei, Anhui Province, China, 230601.
Gang
G
Zong
Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 678 Fu Rong Road, Hefei, Anhui Province, China, 230601.|Cerebral Vascular Disease Research Center, Anhui Medical University, 678 Fu Rong Road, Hefei, Anhui Province, China, 230601.
Hong-Liang
HL
Wang
Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 678 Fu Rong Road, Hefei, Anhui Province, China, 230601.|Cerebral Vascular Disease Research Center, Anhui Medical University, 678 Fu Rong Road, Hefei, Anhui Province, China, 230601.
Er-Bao
EB
Bian
Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, 678 Fu Rong Road, Hefei, Anhui Province, China, 230601. aydzhb@126.com.|Cerebral Vascular Disease Research Center, Anhui Medical University, 678 Fu Rong Road, Hefei, Anhui Province, China, 230601. aydzhb@126.com.
Bing
B
Zhao
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D053781:Transforming Growth Factor beta2 / Q000235:genetics; D015854:Up-Regulation; D055815:Young Adult
C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; C509041:TGFB2 protein, human; D053781:Transforming Growth Factor beta2; C000619854:long non-coding RNA ATB, human
ATB; Glioma; TGF-β2; ceRNA; lncRNA; miR-200a; miRNA