Silencing lncRNA FOXD2-AS1 inhibits proliferation, migration, invasion and drug resistance of drug-resistant glioma cells and promotes their apoptosis via microRNA-98-5p/CPEB4 axis

Abstract

Objective: This study was conducted to elucidate the long non-coding RNA FOXD2-AS1 (lncRNA FOXD2-AS1) expression in glioma and its mechanism on the biological features of glioma cells and the drug resistance of temozolomide (TMZ).Results: Highly expressed FOXD2-AS1 was found in glioma. There was more powerful chemotherapeutic resistance of TMZ resistant cell lines than that of the parent cell lines. Silence of FOXD2-AS1 suppressed proliferation and drug resistance and promoted apoptosis of drug-resistant glioma cells. Overexpressed FOXD2-AS1 presented an opposite trend. FOXD2-AS1 could be used as a competing endogenous RNA to adsorb miR-98-5p, thereby up-regulating CPEB4.Conclusion: Our study suggests that down-regulated FOXD2-AS1 repressed invasion, proliferation, migration and drug resistance of drug-resistant glioma cells while stimulating their apoptosis via increasing miR-98-5p and inhibiting CPEB4 expression.Methods: FOXD2-AS1, microRNA-98-5p (miR-98-5p) and cytoplasmic polyadenylation element binding (CPEB4) expression in glioma tissues were tested. Expression of E-cadherin, N-cadherin and Vimentin in glioma cells were explored. A series of assays were conducted to detect the function of FOXD2-AS1 in migration, proliferation, apoptosis, and invasion of glioma cells. Changes in drug-resistance of cells under TMZ treatment were examined, and tumor formation in nude mice was performed to test the changes of drug resistance in vivo.

MSC-AS1 knockdown inhibits cell growth and temozolomide resistance by regulating miR-373-3p/CPEB4 axis in glioma through PI3K/Akt pathway

“…Similarly, down-regulation of CPEB4 could inhibit cell proliferation and viability, elevate apoptosis and TMZ sensitivity, and affect the PI3K/Akt pathway-related proteins, whereas these effects were overturned by miR-373-3p inhibition. Our results were consistent with previous studies, in which Gu et al showed that FOXD2-AS1 deficiency can hinder cell proliferation and TMZ resistance and promote apoptosis in TMZ-resistant glioma cells by up-regulating miR-98-5p and decreasing CPEB4 [41], and we revealed that MSC-AS1 knockdown could impede cell proliferation, viability, and TMZ resistance and facilitate apoptosis by increasing miR-373-3p and reducing CPEB4 in vitro and in vivo through activating PI3K/Akt pathway.…”

Detailed Molecular Mechanism and Potential Drugs for COL1A1 in Carboplatin-Resistant Ovarian Cancer

“…We also performed real-time PCR and KmPlot analysis to further confirm that the ceRNA network was LINC00052/SMCR5-miR-98-COL1A1 ( Figure 6 ). Moreover, COL1A1 was previously found to be regulated by miR-98 in hypertrophic scarring ( 32 ) and muscular dystrophies ( 33 ); overexpression of miR-98 could increase cell apoptosis and enhance sensitivity to cisplatin in lung adenocarcinoma ( 34 ); and low miR-98 expression was correlated with temozolomide resistance of glioma ( 35 ). Although there have been no reports on the relationship between LINC00052/SMCR5 and chemoresistance, high expression of LINC00052 was found to promote gastric cancer cell proliferation and metastasis ( 36 ) and progression of head and neck squamous cell carcinoma ( 37 ).…”

The role of FOXD2-AS1 in cancer: a comprehensive study based on data mining and published articles

“…Moreover, in glioma, Dong et al [ 36 ] found that FOXD2-AS1 can act as an endogenous sponge of miR-185, which can bind AKT1 to promote cell proliferation and metastasis. In other cancers, FOXD2-AS1 has been suggested to contribute to migration and invasion of tumors by sponging miR-185-5p [ 15 , 28–30 , 36 , 38 , 40 , 46 ], miR-25-3p [ 20 ], miR-98-5p [ 47 ], miR-31 [ 48 ], miR-7-5p [ 49 ], miR-760 [ 44 ], miR-195 [ 24 ], miR-145-5p [ 25 ], miR-363-5p [ 13 , 17 ], miR-143 [ 50 ], miR-485-5p [ 37 ], and miR-206 [ 14 ]. Recent work has shown that lncRNAs influence the occurrence and development of tumors by regulating gene expression at the transcriptional or post-transcriptional level.…”