HOTAIR enhanced paclitaxel and doxorubicin resistance in gastric cancer cells partly through inhibiting miR‐217 expression

Abstract

Drug resistance is a big obstacle for clinical anti-tumor treatment outcome. However, the role of HOTAIR in drug resistance in gastric cancer (GC) remains unknown. In this study, we showed that overexpression of HOTAIR enhanced paclitaxel and doxorubicin resistance in GC cells. Furthermore, the expression of HOTAIR was upregulated in GC tissues and higher expression of HOTAIR was associated with late stage. In addition, we showed that miR-217 expression was lower in GC tissues compared with the paired non-tumour tissues and downregulated expression of miR-217 was correlated with late stage. Interestingly, the expression of miR-217 was negatively correlated with HOTAIR expression in GC tissues. Ectopic expression of HOTAIR increased GC cell proliferation, cell cycle, and migration. Elevated expression of HOTAIR suppressed miR-217 expression and enhanced GPC5 and PTPN14 expression. Furthermore, we demonstrated that overexpression of miR-217 suppressed paclitaxel and doxorubicin resistance in GC cells. Ectopic expression of HOTAIR promoted drug resistance and increased GC cell proliferation, cell cycle, and migration by targeting miR-217. These data suggested that overexpression of HOTAIR enhanced paclitaxel and doxorubicin resistance in GC cells through inhibiting miR-217 expression.

PTPN14, a target gene of miR‐4295, restricts the growth and invasion of osteosarcoma cells through inactivation of YAP1 signalling

“…A recent study reported that PTPN14 overexpression promotes the proliferation and migration of gastric cancer cells 37 . Moreover, PTPN14 overexpression contributes to the paclitaxel and doxorubicin resistance of gastric cancer cells 38 . These studies indicate that the precise PTPN14 function in tumourigenesis may be cancer‐type dependent.…”

Hotair mediates tumorigenesis through recruiting EZH2 in colorectal cancer

“…EZH2 is a highly conserved histone methyltransferase that targets lysine-27 of histone H3, which mediates epigenetic regulation in disease progression. Besides severing as a scaffold protein, Hotair was also reported to promote drug resistance in gastric cancer cells partly through inhibiting miR-217 expression 33 , and it also contributes to liver cancer via targeting miR-217. 31 In addition, EZH2 was induced by vascular endothelial growth factor (VEGF) in endothelial cells and thus promoted tumor angiogenesis.…”

Noncoding RNAs in gastric cancer: implications for drug resistance

“…Multiple onco-lncRNAs, such as HOTAIR, CASC9, MRUL, UCA1, D63785, NEAT1 and HULC, are involved in ADR resistance in gastric cancer (Table 9). For example, via inhibiting miR-217 expression, lncRNA HOTAIR can promote ADR resistance of gastric cancer cells [182]. LncRNA cancer susceptibility candidate 9 (CASC9), whose expression is associated with poor differentiation, invasion and lymph node metastases of gastric cancer, has been reported to promote resistance to ADR of gastric cancer cells through up-regulating expression of MDR1 protein [183].…”

“…Several miRNAs, lncRNAs and circRNAs have been found to be involved in gastric cancer drug resistance by influencing apoptosis, DNA repair, cell cycle, proliferation, autophagy, epithelial-mesenchymal transition, and cancer stem cell through regulating expression of potential target genes and related signaling pathway [175]. In addition, lncRNAs PVT1 [177], HOTAIR [182] and CASC9 [183] also promoted PTX resistance of gastric cancer through modulating expression of various genes.…”