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.

Long noncoding RNA DQ786243 interacts with miR‐506 and promotes progression of ovarian cancer through targeting cAMP responsive element binding protein 1

“…For example, lncRNA MALAT1 was reported to directly bind to miR-204 and upregulated its target gene CXCR4 in hilar cholangiocarcinoma. 21 In this study, our data indicated that DQ786243 promoted ovarian cancer-cell growth through miR-506dependent CREB1 regulation. 20 Moreover, lncRNA CASC2 could interact with miR-181a to modulate glioma growth through PTEN pathway.…”

“…20,21,27,28 Therefore, we further investigated whether miR-506 could directly regulate CREB1 in ovarian cancer. 20,21,27,28 Therefore, we further investigated whether miR-506 could directly regulate CREB1 in ovarian cancer.…”

Long noncoding RNA CASC2 predicts the prognosis of glioma patients and functions as a suppressor for gliomas by suppressing Wnt/β-catenin signaling pathway

“…Recently, CASC2 was reported to be involved in some classical signaling pathways to function as a tumor suppressor 11,19. Wnt/β-catenin signaling pathway is a highly conserved molecular mechanism which was reported to play a crucial role in a variety of human malignancies, including ovarian cancer, hepatocellular carcinoma, breast cancer, and colorectal cancer, by activating its downstream targets including Cyclin D1, c-Myc, GSK-3, and so on 20–23.…”

Low Expression of LncRNA Cancer Susceptibility Candidate 2 and its Clinical Significance in Cancer Tissues

“…These cancers ranged from an early stage to advanced clinical stages (I, II, III, and IV). Of the 8 studies, 3 included a follow-up of greater than or equal to 60 months [23, 27, 28]; the remaining 5 studies covered less than 5 years [21, 22, 24-26]. The expression of lncRNA CASC2 in all eligible studies was measured by quantitative real-time polymerase chain reaction (qRT-PCR) and normalized relative to GAPDH or RNU6B using the 2 –ΔΔCt method.…”