Preprint Communication Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 8 July 2020 / Approved: 9 July 2020 / Online: 9 July 2020 (12:30:11 CEST)

How to cite: Namgail, T.; Kumar, D.; Vashistha, V.; Aquib, A.; Yadav, A. HnRNPA1 and Its Effect in the Expression of ABCC (ABCC4 and ABCC6) Transporter in Glioma Cell Lines. Preprints 2020, 2020070193 (doi: 10.20944/preprints202007.0193.v1). Namgail, T.; Kumar, D.; Vashistha, V.; Aquib, A.; Yadav, A. HnRNPA1 and Its Effect in the Expression of ABCC (ABCC4 and ABCC6) Transporter in Glioma Cell Lines. Preprints 2020, 2020070193 (doi: 10.20944/preprints202007.0193.v1).

Abstract

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 factors 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's) 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 was 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.

Subject Areas

hnRNPA1; ABCC

Comments (1)

Comment 1
Received: 2 August 2020
Commenter: Pankaj Taneja
The commenter has declared there is no conflict of interests.
Comment: Chip binding assays should be done for ABCC4 and 6 with oxidative stress molecular markers in normal and tumor cell lines to have insights of it's differential response for understanding detailed mechanisms
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