LINC00883 Promotes Drug Resistance of Glioma Through a microRNA-136/NEK1-Dependent Mechanism

ObjectiveAccumulating evidence has highlighted the roles of long noncoding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) of microRNAs (miRNAs) through their binding sites in the progression of glioma. Hereby, we aim to explore the role of LINC00883 as a regulator of miR-136 and its target, NIMA-related kinase 1 (NEK1), thus, its involvement in the drug resistance of glioma cells.Methods and ResultsMechanistic investigations by dual-luciferase reporter, RNA pull-down, and RNA-binding protein immunoprecipitation (RIP) assays indicated that LINC00883 bound to miR-136, thereby blocking miR-136-induced downregulation of NEK1. Through gain-of-function experiments in U251 cells that presented a high drug resistance, we found that ectopic expression of LINC00883 resulted in increased MRP (encoding multidrug resistance-associated protein), limited cell apoptosis, and increased proliferation. Expectedly, depleting LINC00883 yielded tumor-suppressive and anti-chemoresistance effects on U251 cells by increasing miR-136 and inhibiting NEK1. Next, drug-resistant glioma cell line SOWZ1, drug-sensitive glioma cell line SOWZ2, and drug-resistant glioma cell line SOWZ2-BCNU (SOWZ2 cultured in BCNU) were applied to validate the roles of LINC00883 in the regulation of multidrug resistance. LINC00883 knockdown suppressed the viability of SWOZ1, SWOZ2, and SWOZ2-BCNU cells.ConclusionIn conclusion, LINC00883 knockdown reduces drug resistance in glioma. Hence, our study provides a future strategy to prevent drug resistance-induced therapeutic failure in glioma.

Download Full-text

Reversal of drug resistance mediated by hammerhead ribozyme against multidrug resistance-associated protein 1 in a human glioma cell line

International Journal of Oncology ◽

10.3892/ijo.22.4.823 ◽

2003 ◽

Author(s):

Hideo Osada ◽

Tetsuji Tokunaga ◽

Yoshiyuki Abe ◽

Satomi Asai ◽

Hayato Miyachi ◽

...

Keyword(s):

Drug Resistance ◽

Multidrug Resistance ◽

Cell Line ◽

Glioma Cell ◽

Hammerhead Ribozyme ◽

Glioma Cell Line ◽

Human Glioma ◽

Human Glioma Cell Line ◽

Human Glioma Cell

Download Full-text

Amplification and expression of a multidrug resistance gene in human glioma cell lines

Journal of Neurosurgery ◽

10.3171/jns.1990.72.1.0096 ◽

1990 ◽

Vol 72 (1) ◽

pp. 96-101 ◽

Cited By ~ 23

Author(s):

Tsuyoshi Matsumoto ◽

Eiichi Tani ◽

Keizo Kaba ◽

Nobuo Kochi ◽

Hideki Shindo ◽

...

Keyword(s):

Multidrug Resistance ◽

Cell Line ◽

Cell Lines ◽

Glioma Cell ◽

Multidrug Resistant ◽

Glioma Cell Line ◽

Cross Resistance ◽

Human Glioma ◽

Human Glioma Cell ◽

Glioma Cell Lines

✓ Two human glioma cell lines were examined for multidrug resistance (MDR). A vincristine (VCR)-resistant glioma cell line showed a cross resistance to Adriamycin (doxorubicin, ADR) and etoposide (VP-16) to varying extents, suggesting the presence of MDR; the resistance to VCR was considerably decreased by calcium entry blockers. On the other hand, another VCR-sensitive glioma cell line exhibited no cross resistance to ADR or VP-16. Double minute chromosomes and homogeneously staining regions as well as clonal aberrations of chromosome 7 were not observed in cytogenetic studies of multidrug-resistant and multidrug-sensitive glioma cell lines. In Northern and Southern blot analyses, MDR gene 1 (MDR1) messenger ribonucleic acid (mRNA) was shown to be overexpressed without any amplification of the MDR1 gene in multidrug-resistant glioma cell lines as compared to multidrug-sensitive glioma cell lines. It would be reasonable to suggest that amplification of the MDR1 gene may not be a sine qua non for acquisition of MDR and that the MDR1 mRNA level may be well correlated with the extent of MDR.

Download Full-text

Effect and mechanism of peroxisome proliferator-activated receptor-γ on the drug resistance of the U-87 MG/CDDP human malignant glioma cell line

Molecular Medicine Reports ◽

10.3892/mmr.2015.3625 ◽

2015 ◽

Vol 12 (2) ◽

pp. 2239-2246 ◽

Cited By ~ 4

Author(s):

SHAORONG HAN ◽

XIAOYAN LV ◽

YANMING WANG ◽

HAI GONG ◽

CONG ZHANG ◽

...

Keyword(s):

Drug Resistance ◽

Malignant Glioma ◽

Cell Line ◽

Glioma Cell ◽

Glioma Cell Line ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Human Malignant Glioma

Download Full-text

HnRNPA1 and Its Effect in the Expression of ABCC (ABCC4 and ABCC6) Transporter in Glioma Cell Lines

10.20944/preprints202007.0193.v1 ◽

2020 ◽

Author(s):

Tundup Namgail ◽

Dinesh Kumar ◽

Vidhi Vashistha ◽

Ahmed Aquib ◽

Ajay Yadav

Keyword(s):

Drug Resistance ◽

Brain Tumor ◽

Alternative Splicing ◽

Cell Line ◽

Reverse Transcription ◽

Glioma Cell ◽

Glioma Cell Line ◽

Splicing Factor ◽

Glioma Cell Lines ◽

Alternative Splicing Factor

Glioblastoma multiforme (GBM) is classified as WHO grade IV Astrocytoma & is the most common highly aggressive form of primary brain tumor. Garde IV tumor are highly recurrent even after treatment, with patient survival rate is less than two years from the time of diagnosis. This might be due to overexpression of one of the factor such as ATP-binding cassette transporters (ABC transporters) responsible for drug resistance. ABCC transporter family a member of ABC transporter was found to mostly responsible for multi drug resistance (MDR) in cancer cells. On the other hand, heterogeneous nuclear ribonucleoprotein (hnRNP) an alternative splicing factor play different role in various cellular process such as nucleic acid metabolism, transcription and translation regulation, among them hnRNPA1 is best studied and its aberrant deregulation favor development of cancer. This study was focused on to study the function of hnRNPA1 in the expression analysis of ABCC transporter (responsible for MDR) in glioma cell lines. The expression of ABCC transporter (ABCC4 and ABCC6) gene was examined in two glioma cell line i.e. U87MG and T98G in normal and knockdown two alternative variants of hnRNPA1 by Quantitative Realtime PCR and Reverse Transcription PCR. We found that ABCC4 was significantly overexpressed in hnRNPA1 Variant 2 knockdown cells (si hnRNPA1 V2) in U87 (3-fold) and in T98G (18.34-fold), While hnRNPA1 Variant 1 knockdown cells (hnRNPA1 V1i) does not shows any significant effect. Further, the expression of ABCC6 was decreased in both hnRNPA1 V1i (0.40-fold) and hnRNPA1 V2i (0.48-fold) in U87. Reverse transcription based result were complemented with normal PCR based detection strategy after running in agarose gel for U87MG and T98G glioma cell line. Finally, this result indicates that hnRNPA1 an alternative splicing factor regulate the expression of ABCC4 and ABCC6 transporter which are responsible for multiple drug resistance in cancer. This information will help in future for the development of an alternative method for the treatment of drug resistance cases in brain tumor and other tumors by targeting hnRNPA1 splicing factor.

Download Full-text