<p>lncRNA CCAT2 Enhanced Resistance of Glioma Cells Against Chemodrugs by Disturbing the Normal Function of miR-424</p>

Abstract

These authors contributed equally to this workBackground: Aggressive metastasis of tumor cells assumed a constructive role in strengthening chemoresistance of tumors, so this investigation was intended to elucidate if lncRNA CCAT2 sponging downstream miR-424 regulated chemotolerance of glioma cells by boosting metastasis of glioma cells. Methods: One hundred and twenty-eight pairs of glioma tissues and corresponding adjacent tissues were resected from glioma patients during their operation, and we also purchased a series of glioma cell lines, including U251, U87, A172 and SHG44. Furthermore, pcDNA3.1-CCAT2, si-CCAT2, miR-424 mimic and miR-424 inhibitor were transfected into SHG44 and U251 cell lines, so as to evaluate impacts of CCAT2 and miR-424 on chemosensitivity of the glioma cells. Besides, proliferation, invasion and metastasis of the cells were determined through the implementation of colony formation assay, transwell assay and scratch assay. Results: Glioma tissues and cells were monitored with higher CCAT2 expression and lower miR-424 expression than adjacent normal tissues and NHA cell line (P<0.05). Among the glioma cell lines, the SHG44 cell line showed the strongest resistance against teniposide, temozolomide and cisplatin (P<0.05), whereas the U251 cell line was more sensitive to teniposide, temozolomide, vincristine and cisplatin than any other cell line (P<0.05). Besides, pcDNA3.1-CCAT2 and miR-424 inhibitor could enhance tolerance of glioma cell lines against drugs (P<0.05). Moreover, in-vitro transfection of si-CCAT2 and miR-424 mimic could significantly retard proliferation, invasion and migration of SHG44 and U251 cells (P<0.05), and CCAT2 was found to negatively regulate miR-424 expression by sponging it (P<0.05). In addition, CHK1 was deemed as the molecule targeted by upstream miR-424, and its overexpression can changeover the effects of miR-424 mimic on proliferation and metastasis of SHG44 and U251 cells. Conclusion: lncRNA CCAT2/miR-424/Chk1 axis might serve as a promising target for improving chemotherapeutic efficacies in glioma treatment.

Long Non-Coding RNAs in Diagnosis, Treatment, Prognosis, and Progression of Glioma: A State-of-the-Art Review

“…Determining treatment response : lncRNAs modulate treatment response by affecting sensitivity to chemotherapy drugs, mainly TMZ or cisplatin, or altering radiosensitivity. Higher NEAT1 ( 151 , 160 ), XIST ( 172 ), FOXD2-AS1 ( 189 , 192 ), TP73-AS1 ( 251 ), CCAT2 ( 252 ), and lncSBF2-AS1 ( 241 ) were associated with TMZ-resistance. These effects are mediated via several mechanisms.…”

“…In another example, FOXD2-AS1 reduced methylation and increased activity of O 6 -methylguanine-DNA methyltransferase (MGMT), which is a treatment response predictor in glioma ( 192 ). Furthermore, cisplatin resistance was associated with higher levels of DANCR ( 253 ), CRNDE ( 178 ), CCAT2 ( 252 ), and lower levels of GAS5 ( 216 ). Additionally, overexpression of XIST reduced radiosensitivity ( 167 ), while high expression of DRAIC was associated with a better prognosis of radiotherapy in low-grade glioma ( 254 ).…”

Long non-coding RNAs in brain tumors: roles and potential as therapeutic targets

“…CCAT2 also acts as a molecular sponge to downregulate miR-424 and upregulates Chk1, thereby enhancing chemotolerance in glioma cells [ 137 ].…”

Long Non-Coding RNAs in Multidrug Resistance of Glioblastoma

“…Thus, silencing LINC00461 led to remarkable chemosensitization in glioblastoma cells [ 117 ]. CCAT2 by sponging miR-424 [ 118 ], XIST by targeting miR-29c [ 119 ], NCK1-AS1 by targeting miR-137 [ 120 ], SNHG15 by targeting miR-627 [ 106 ], DLEU2 by targeting miR-186-5p [ 121 ], and FOXD2 by sponging miR-98-5p [ 122 ] play a major role in the promoting cell proliferation and invasion and developing MDR against temozolomide in glioblastoma cells ( Figure 4 ).…”