Abstract
LMX1A (LIM homeobox transcription factor 1α) is a tumor suppressor protein. Our previous study has shown that microRNA-9 (“miR-9”), being upregulated in human gastric cancer (GC), targets LMX1A to promote GC cell progression. Through searching long non-coding RNA (LncRNA) database, we identified that LncRNA KCNQ1OT1 is the competing endogenous RNA (ceRNA) of miR-9. KCNQ1OT1 putatively targets miR-9. Its level is downregulated in human GC tissues. In AGS cells and primary human GC cells, forced overexpression of KCNQ1OT1, by a lentiviral construct, induced miR-9 downregulation and LMX1A upregulation. Furthermore, KCNQ1OT1 overexpression inhibited GC cell survival, proliferation, migration and invasion, but inducing apoptosis activation. Contrarily, KCNQ1OT1 silencing, by targeted siRNAs, induced miR-9 accumulation and LMX1A downregulation. Consequently, GC cell proliferation, migration and invasion were enhanced. Importantly, KCNQ1OT1 overexpression or silencing was ineffective in LMX1A knockout AGC cells. Taken together, KCNQ1OT1 inhibits GC cell progression via regulating miR-9 and LMX1A expression.
Highlights
Gastric cancer (GC) is a common cancer, causing significant human mortalities each year [1]
long non-coding RNA (LncRNA) KCNQ1OT1 is downregulated in human GC tissues
It is possible that miR-9 upregulation in GC could be due to downregulation of certain LncRNAs
Summary
Gastric cancer (GC) is a common cancer, causing significant human mortalities each year [1]. We found that LMX1A inhibited c-Myc expression to exert tumor suppressive function in GC cells [6]. We show that miR-9 selectively targets and negatively regulates LMX1A to promote GC cell progression [7]. Accumulative studies have confirmed that dysregulation of LncRNA plays a pivotal role in the progression of GC [15, 16] and other human cancers [17, 18]. One aim of this study is to identify possible miR-9-targeting LncRNA, regulating LMX1A expression and GC cell functions. Recent studies have shown that KCNQ1OT1 dysregulation participates in carcinogenesis and progression of human cancers [21, 22]. We will show that LncRNA KCNQ1OT1 inhibits GC cell progression possibly via regulating miR-9 and LMX1A expression
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