Overexpression of lncRNA NEAT1 mitigates multidrug resistance by inhibiting ABCG2 in leukemia

Abstract

Abstract. Leukemia is a heterogeneous clonal disorder in which early hematopoietic cells fail to differentiate and do not undergo programmed cell death or apoptosis. Less than one-third of adult patients with leukemia are managed using current therapies due to the emergence of multidrug resistance (MDR), emphasizing the need for newer and more robust approaches. Recent reports have suggested that long non-coding RNAs (lncRNAs) contribute to selective gene expression and, hence, could be manipulated effectively to halt the progression of cancer. However, little is known regarding the role of lncRNA in leukemia. Nuclear paraspeckle assembly transcript 1 (NEAT1) is a nuclear-restricted lncRNA involved in the pathogenesis of certain types of cancer. Deregulated expression of NEAT1 has been reported in a number of human malignancies, including leukemia and other solid tumors. The present study aimed to characterize the role of NEAT1 in the regulation of MDR in leukemia. Using reverse transcription-quantitative polymerase chain reaction, it was demonstrated that NEAT1 messenger RNA (mRNA) expression levels were significantly downregulated in leukemia patient samples compared with those from healthy donors. Furthermore, NEAT1 mRNA expression was repressed in a number of leukemia cell lines, including K562, THP-1, HL-60 and Jurkat cells, compared with peripheral white blood control cells, consistent with the expression observed in patients with leukemia. In addition, the transfection of a NEAT1 overexpression plasmid into K562 and THP-1 leukemia cell lines alleviated MDR induced by cytotoxic agents, such as Alisertib and Bortezomib, through inhibition of ATP-binding cassette G2. Although more robust studies are warranted, the current findings provide the basis for the use of NEAT1 as a novel promising target in the treatment of leukemia.

LncRNA NEAT1 contributes to paclitaxel resistance of ovarian cancer cells by regulating ZEB1 expression via miR-194

“… 24 NEAT1 expression level was downregulated in leukemia patients and cells and overexpression of NEAT1-mitigated MDR induced by cytotoxic agent through inhibition of ATP-binding cassette G2 (ABCG2) in leukemia. 25 Another study reported that NEAT1 enhanced cisplatin sensitivity in non-small-cell lung cancer through functioning as a ceRNA to upregulate EGCG-induced cisplatin transporter CTR1 (copper transporter 1) by sponging miR-98-5p. 26 In the present study, it is demonstrated that NEAT1 was upregulated in PTX-resistant ovarian cancer tissues and cells.…”

Non-coding RNA NEAT1/miR-214-3p contribute to doxorubicin resistance of urothelial bladder cancer preliminary through the Wnt/β-catenin pathway

“… 20 NEAT1 dys-regulated in ovarian cancer, lung cancer, gastric cancer and leukemia were reported to contribute to the chemotherapy resistance of paclitaxel, cisplatin, adriamycin, alisertib and bortezomib. 14 , 21 – 23 LncRNA PVT1, TUG1 and UCA1 were reported to upregulate in UBC, especially in the doxorubicin and cisplatin-resistant UBC tissues and cell lines. Forced lncRNA-LET expression delayed gemcitabine-induced tumor recurrence.…”

Long non-coding RNA NEAT1 contributes to docetaxel resistance of prostate cancer through inducing RET expression by sponging miR-34a

“…For example, NEAT1 expression was found to be repressed in leukemia cells and overexpression of NEAT1 alleviated multidrug resistance in leukemia cells through inhibition of ATPbinding cassette G2. 35 NEAT1 was demonstrated to function as a ceRNA of miR-98-5p to upregulate copper transporter 1 (CTR1), thus enhancing cisplatin sensitivity in lung cancer cells. 36 Additionally, NETA1 was reported to be highly expressed in gastric cancer tissues and cells, moreover, NEAT1 knockdown depressed chemotherapy resistance to adriamycin and promoted adriamycin-induced apoptosis in gastric cancer.…”