Research Paper Volume 12, Issue 1 pp 707—717

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

Li Feng 1, *, , Huanqin Li 1, *, , Fan Li 1, *, , Songhua Bei 1, , Xiaohong Zhang 1, ,

  • 1 Endoscopy Center, Minhang Hospital, Fudan University, Shanghai, China
* Equal contribution

received: August 28, 2019 ; accepted: December 24, 2019 ; published: January 8, 2020 ;

https://doi.org/10.18632/aging.102651
How to Cite

Copyright © 2020 Feng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.

Abbreviations

CCK-8: Cell Counting kit-8; ceRNA: competing endogenous RNA; EdU: (5-ethynyl-20-deoxyuridine); GC: gastric cancer; LMX1A: LIM homeobox transcription factor 1α; LncRNA: long non-coding RNA; miR-9: microRNA-9; ncRNAs: non-coding RNAs; Kcnq1: potassium voltage-gated channel subfamily Q member 1; qPCR: quantitative reverse transcriptase PCR; SD: standard deviation.