Long noncoding RNA BLACAT1 modulates ABCB1 to promote oxaliplatin resistance of gastric cancer via sponging miR-361.

Long non-coding RNAs (lncRNAs) have emerged as novel gene regulators in multiple tumorigenesis and chemoresistance. However, their potential roles and molecular mechanisms in gastric cancer chemoresistance remain unclear. In present study, our team investigated the role and potential regulatory mechanism of lncRNA s bladder cancer associated transcript-1 (BLACAT1) in the gastric cancer chemoresistance. Results showed that BLACAT1 expression was up-regulated in the oxaliplatin (OXA) resistant gastric cancer tissue and cells compared with OXA-sensitive tissue and parental cell lines. In vitro, BLACAT1 knockdown decreased the expression levels of drug resistance related genes and ABCB1 protein. Besides, BLACAT1 knockdown significantly promoted apoptosis and down-regulated the invasion and the IC50 value of oxaliplatin. In vivo, BLACAT1 knockdown suppressed the tumor growth of gastric cancer cells. Bioinformatics tools and luciferase assay indicated that miR-361 both targeted 3?-UTR of BLACAT1 and ABCB1mRNA, suggesting the BLACAT1/miR-361/ABCB1 regulatory pathway. In summary, our results conclude that BLACAT1 accelerates the oxaliplatin-resistance of gastric cancer via promoting ABCB1 protein expression by targeting miR-361, providing a novel insight for the chemoresistance of gastric cancer.

Wu X ，Zheng Y ，Han B ，Dong X ... -  《-》

Long non-coding RNA LUCAT1 modulates methotrexate resistance in osteosarcoma via miR-200c/ABCB1 axis.

Long non-coding RNAs (lncRNAs) have been verified to participate in the tumorigenesis of multiple cancers. Nevertheless, the deepgoing role molecular mechanisms of lncRNAs on osteosarcoma chemoresistance remain unclear. In present study, we investigate the function of lncRNA LUCAT1 on osteosarcoma methotrexate (MTX) resistant phenotype and discover the potential regulatory mechanism. Results showed that LUCAT1 was up-regulated in MTX-resistant cells (MG63/MTX, HOS/MTX) compared to that in parental cells. LncRNA LUCAT1 and ABCB1 protein expression levels were both up-regulated when induced by different concentration of methotrexate. In vitro and vivo, LUCAT1 knockdown decreased the expression levels drug resistance related genes (MDR1, MRP5, LRP1), proliferation, invasion and tumor growth of osteosarcoma cells. Bioinformatics tools and luciferase assay reveled that miR-200c both targeted the 3'-UTR of LUCAT1 and ABCB1 mRNA, suggesting the modulation of LUCAT1 on ABCB1 through sponging miR-200c. Rescue experiments confirmed the combined role of LUCAT1, miR-200c and ABCB1 on osteosarcoma proliferation, invasion and methotrexate resistance. Overall, results indicate the vital role of LUCAT1 in the methotrexate resistance regulation through miR-200c/ABCB1 pathway, providing a novel insight and treatment strategy for osteosarcoma drug resistance.

Han Z ，Shi L 《-》

Long Noncoding RNA Bladder Cancer Associated Transcript 1 Promotes the Proliferation, Migration, and Invasion of Nonsmall Cell Lung Cancer Through Sponging miR-144.

Ye JR ，Liu L ，Zheng F 《-》

Knockdown of long non-coding RNA HOTAIR inhibits cisplatin resistance of gastric cancer cells through inhibiting the PI3K/Akt and Wnt/β-catenin signaling pathways by up-regulating miR-34a.

HOX transcript antisense RNA (HOTAIR), a well-known long non-coding RNA (lncRNA), has been reported to be related to cisplatin (DDP) resistance in gastric cancers. However, the molecular mechanism of HOTAIR in DDP resistance of gastric cancer (GC) remains largely undefined. The aim of this study was to investigate the role and underlying mechanism of HOTAIR in regulating cisplatin resistance of GC. The results showed that HOTAIR was over-expressed in GC tissues and GC cell lines, while miR-34a was low-expressed. Luciferase reporter assay and RIP assay proved that HOTAIR directly bound to miR-34a. MiR-34a expression was significantly increased in si-HOTAIR-transfected cells. Anti-miR-34a reversed the effect of si-HOTAIR on the DDP resistance, apoptosis-related genes, PI3K/Akt and Wnt/β-catenin signaling pathways in DDP-resistant GC cells, indicating that the effects of HOTAIR are dependent on miR-34a. In addition, knockdown of HOTAIR enhanced DDP inhibitory effect on tumor growth in vivo. In conclusion, HOTAIR knockdown inhibited DDP resistance of gastric cancer cells by upregulating miR-34a. The effect of HOTAIR/miR-34a axis on GC cells may be involved in the PI3K/Akt and Wnt/β-catenin signaling pathways. The results indicated that HOTAIR might be a new potential target in GC therapy.

Cheng C ，Qin Y ，Zhi Q ，Wang J ，Qin C ... -  《-》

miR-135a promotes gastric cancer progression and resistance to oxaliplatin.

Yan LH ，Chen ZN ，Li-Li ，Chen J ，Wei WE ，Mo XW ，Qin YZ ，Lin Y ，Chen JS ... -  《Oncotarget》