Research Paper Volume 11, Issue 23 pp 11358—11368

LINC00682 inhibits gastric cancer cell progression via targeting microRNA-9-LMX1A signaling axis

Xiaohong Zhang 1, *, , Jian Li 1, *, , Fan Li 1, *, , Zhen Zhao 2, , Li Feng 1, ,

  • 1 Endoscopy Center, Minhang Hospital, Fudan University, Shanghai, China
  • 2 Department of Clinical Laboratory, Minhang Hospital, Fudan University, Shanghai, China
* Equal contribution

received: September 7, 2019 ; accepted: November 18, 2019 ; published: December 11, 2019 ;

https://doi.org/10.18632/aging.102533
How to Cite

Copyright © 2019 Zhang 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

microRNA-9 (“miR-9”), upregulated in human gastric cancer (GC) tissues, targets LMX1A (LIM homeobox transcription factor 1α) to promote GC cell progression. The underlying mechanism of miR-9 upregulation in GC is still unknown. Through searching multiple long non-coding RNA (LncRNA) databases, we here discovered that the long non-coding RNA LINC00682 (long intergenic non-protein coding RNA 682) putatively targets miR-9. We show that ectopic overexpression of LINC00682 induced miR-9 downregulation but LMX1A upregulation, inhibiting AGS cell survival, proliferation, migration and invasion. Significant apoptosis activation was detected in LINC00682-overexpressed AGS cells. Contrarily, LINC00682 knockdown induced miR-9 upregulation but LMX1A downregulation, promoting AGS cell survival, proliferation, migration and invasion. In the primary human GC cells, forced LINC00682 overexpression similarly induced miR-9 downregulation and LMX1A upregulation, causing proliferation inhibition and apoptosis activation. Significantly, restoring miR-9 expression by a lentiviral construct reversed LINC00682-induced actions in GC cells. Furthermore, LINC00682 was ineffective in LMX1A KO AGS cells. Importantly, LINC00682 expression levels are significantly downregulated in human GC tissues. We conclude that LINC00682 inhibits GC cell progression via targeting miR-9-LMX1A signaling axis.

Abbreviations

EdU: 5-ethynyl-20-deoxyuridine; GC: gastric cancer; LMX1A: LIM homeobox transcription factor 1α; LncRNA: Long non-coding RNAs; LINC00682: long intergenic non-protein coding RNA 682; miR-9: microRNA-9; PARP: poly (ADP-ribose) polymerase; siRNA: small interfering RNA; SD: standard deviation; OD: optical density; TUNEL: terminal deoxynucleotidyl transferase dUTP nick-end labeling.