Silencing of long non-coding RNA ANRIL inhibits the development of multidrug resistance in gastric cancer cells

Abstract

The development of multidrug resistance (MDR) is a crucial cause of therapy failure in gastric cancer, which results in disease recurrence and metastasis. Long non-coding RNAs (lncRNAs) have been proven to be critical in carcinogenesis and metastasis of gastric cancer. However, little is known about the roles of ANRIL (antisense non-coding RNA in the INK4 locus) in gastric cancer MDR. The aim of our study is to identify the biological function of ANRIL in gastric cancer MDR. In our results, ANRIL was highly expressed in gastric cancer tissues of cisplatin-resistant and 5-fluorouracil (5-FU)-resistant patients, and the same upregulation trends were observed in cisplatin-resistant cells (BGC823/DDP) and 5-FU-resistant cells (BGC823/5-FU). In addition, BGC823/DDP and BGC823/5-FU cells transfected with ANRIL siRNA and treated with cisplatin or 5-FU, respectively, exhibited significant lower survival rate, decreased invasion capability, and high percentage of apoptotic tumor cells. The influence of ANRIL knockdown on MDR was assessed by measuring IC50 of BGC823/DDP and BGC823/5-FU cells to cisplatin and 5-FU, the result showed that silencing ANRIL decreased the IC50 values in gastric cancer cells. Moreover, qRT-PCR and western blotting revealed that ANRIL knockdown decreased the expression of MDR1 and MRP1, both of which are MDR related genes; regression analysis showed that the expression of ANRIL positively correlated with the expression of MDR1 and MRP1, resprectively In summary, knockdown of lncRNA ANRIL in gastric cancer cells inhibits the development of MDR, suggesting an efficacious target for reversing MDR in gastric cancer therapy.

LncRNA FENDRR attenuates adriamycin resistance via suppressing MDR1 expression through sponging HuR and miR‐184 in chronic myelogenous leukaemia cells

“…Next, we detected several known lncRNAs involved in drug resistance in K562 and K562/ADM cells by qRT-PCR, such as HOTAIR [28], PVT1 [29], H19 [10], MALAT1 [30], UCA1 [11], CCAL [31], ANRIL [32], MEG3 [33] and FENDRR [12]. Interestingly, we found that FENDRR was mostly downregulated in K562/ADM cells compared with that in K562 cells ( Fig.…”

Long non-coding RNAs in anti-cancer drug resistance

“…Lan et al found that ANRIL was greatly upregulated in cisplatin resistant and 5-Fu resistant patients. The rate of tumor growth significantly decreased after transfected with si-ANRIL, and the levels of MDR1, MRP1 also reduced [74]. …”

Noncoding RNAs in gastric cancer: implications for drug resistance

“…LncRNA SNHG5 reduced DDP sensitivity of BGC823 and SGC7901 gastric cancer cells through up-regulating expression of MDR1, MRP1 and Bax as well as downregulating Bcl-2 expression [164]. In addition, lncRNAs GHET 1 [165], AK022798 [166], antisense non-coding RNA in the INK4 locus (ANRIL) [167], UCA 1 [168] and HULC [169] also conferred DDP resistance of gastric cancer cells via modulating expression of multiple drug resistance-related genes. LncRNA HOTAIR, which was significantly up-regulated in DDPresistant gastric cancer cells and tissues, could regulate chromatin status and contribute to DDP resistance of gastric cancer, through activating PI3K/Akt/MRP1 and Wnt/ β-catenin signaling pathways [170,171].…”