title: LncRNA CASC2 Interacts With miR-181a to Modulate Glioma Growth and Resistance to TMZ Through PTEN Pathway.
abstract: Temozolomide (TMZ)-based chemotherapy is a standard strategy for glioma, while chemoresistance remains a major therapeutic challenge. Recent evidence highlights the crucial regulatory roles of long non-coding RNAs (lncRNA) in tumor biology. However, the roles and regulatory mechanisms of lncRNA cancer susceptibility candidate 2 (CASC2), in glioma tumorigenesis and chemoresistance are poorly understood. In this study, CASC2 expression was down-regulated in glioma tissues and cell lines, and was related to a clinicopathologic features and shorter survival time. Exogenous CACS2 alone was sufficient to inhibit glioma cells' proliferation and amplified TMZ-induced repression of cell proliferation, while CACS2 knockdown could reverse this process. CACS2 overexpression could sensitize TMZ-resistant glioma cells to TMZ, while CACS2 knockdown exerted the opposite function. Moreover, CASC2 could inhibit the miR-181a expression by direct targeting in TMZ-resistant glioma cells. CASC2 up-regulated PTEN protein and down-regulated p-AKT protein through regulating miR-181a, and the effect of CASC2 on PTEN and p-AKT could be partially restored by miR-181a. With TMZ-resistant glioma tissues, miR-181a was up-regulated while PTEN was down-regulated. Taken together, these observations suggest CASC2 up-regulates PTEN through direct inhibiting miR-181a and plays an important role in glioma sensitivity to TMZ and may serve as a potential target for cancer diagnosis and treatment. J. Cell. Biochem. 118: 1889-1899, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University (CSU), Changsha 410008, P. R. China.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University (CSU), Changsha 410008, P. R. China.
authors.forename: Liangfang
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University (CSU), Changsha 410008, P. R. China.
authors.forename: Haiting
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University (CSU), Changsha 410008, P. R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Oncology, Xiangya Hospital, Central South University (CSU), Changsha 410008, P. R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University (CSU), Changsha 410008, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University (CSU), Changsha 410008, P. R. China.
authors.forename: Renjun
authors.initials: R
authors.lastname: Peng
authors.affiliation: Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao 266003, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000328:Adult; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D016016:Proportional Hazards Models; D011485:Protein Binding; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D025521:Tumor Suppressor Proteins; C484713:long non-coding RNA CASC2, human; D003606:Dacarbazine; D051059:PTEN Phosphohydrolase; D000077204:Temozolomide
keywords: CASC2; CHEMO-RESISTANCE; GLIOMA; PTEN; TEMOZOLOMIDE (TMZ); miR-181a