LncRNA CASC2 Interacts With miR‐181a to Modulate Glioma Growth and Resistance to TMZ Through PTEN Pathway

• Published in: Journal of cellular biochemistry 2017-07, Vol.118 (7), p.1889-1899
• Main Authors: Liao, Yiwei, Shen, Liangfang, Zhao, Haiting, Liu, Qing, Fu, Jun, Guo, Yong, Peng, Renjun, Cheng, Lei
• Format: Article
• Language: English
• Subjects: Adult; AKT protein; Amplification; Biochemistry; Biology; Biotechnology; Blotting, Western; Brain tumors; Cancer; CASC2; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Cell Proliferation - genetics; Chemoresistance; Chemotherapy; CHEMO‐RESISTANCE; Coding; Dacarbazine - analogs & derivatives; Dacarbazine - pharmacology; Dacarbazine - therapeutic use; Diagnosis; Female; GLIOMA; Glioma - drug therapy; Glioma - metabolism; Glioma cells; Humans; In Vitro Techniques; Male; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miR‐181a; Multivariate Analysis; Proportional Hazards Models; Protein Binding; PTEN; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; PTEN protein; Real-Time Polymerase Chain Reaction; Regulatory mechanisms (biology); RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Sensitivity; Strategy; Survival; Temozolomide; TEMOZOLOMIDE (TMZ); Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumorigenesis
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.25910

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. In the present study, we have demonstrated that CASC2 plays an important role in the chemo‐resistance of glioma by functioning as a ceRNA to regulate the expression of key genes. CASC2 may potentially act as an effective therapeutic candidate combined with traditional TMZ‐based chemo‐therapy for glioma.