LncRNA KCNQ1OT1 regulates microRNA-9-LMX1A expression and inhibits gastric cancer cell progression

Abstract

LMX1A (LIM homeobox transcription factor 1α) is a tumor suppressor protein. Our previous study has shown that <i>microRNA-9</i> ("<i>miR-9</i>"), being upregulated in human gastric cancer (GC), targets LMX1A to promote GC cell progression. Through searching <i>long non-coding RNA</i> (<i>LncRNA</i>) database, we identified that <i>LncRNA KCNQ1OT1</i> is the <i>competing endogenous RNA</i> (ceRNA) of <i>miR-9. KCNQ1OT1</i> putatively targets <i>miR-9</i>. Its level is downregulated in human GC tissues. In AGS cells and primary human GC cells, forced overexpression of <i>KCNQ1OT1</i>, by a lentiviral construct, induced <i>miR-9</i> downregulation and LMX1A upregulation. Furthermore, <i>KCNQ1OT1</i> overexpression inhibited GC cell survival, proliferation, migration and invasion, but inducing apoptosis activation. Contrarily, <i>KCNQ1OT1</i> silencing, by targeted siRNAs, induced <i>miR-9</i> accumulation and LMX1A downregulation. Consequently, GC cell proliferation, migration and invasion were enhanced. Importantly, <i>KCNQ1OT1</i> overexpression or silencing was ineffective in LMX1A knockout AGC cells. Taken together, <i>KCNQ1OT1</i> inhibits GC cell progression via regulating <i>miR-9</i> and LMX1A expression.