MicroRNA-29a inhibits cell migration and invasion via targeting Roundabout homolog 1 in gastric cancer cells
Authors: Xinmiao He
Shitao Jiang
Yanjun Sun
Xueting Liu
Xingguo Zhong
Enwu Bao
Liusheng Yang
Jun Cai
Renhua Gong
Yongxiang Li
Dengqun Sun
Journal: Molecular Medicine Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: Robo1; miR-29a; gastric cancer; migration; invasion
Affiliations: Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China., Department of General Surgery, Armed Police Corps Hospital of Anhui, Hefei, Anhui 230041, P.R. China.

Abstract:  Deregulation of Roundabout homolog 1 (Robo1) has been demonstrated to be associated with several types of human cancer, including gastric cancer. However, the detailed role of Robo1 and its regulatory mechanism in gastric cancer remain largely unclear. In the current study, it was demonstrated that the expression of microRNA (miR)‚Ä?9a was frequently reduced in gastric cancer tissues, compared with their matched normal adjacent tissues. Similar results were additionally observed in AGS and SGC‚Ä?901 human gastric cancer cells. Overexpression of miR‚Ä?9a led to reduced migration and invasion of AGS cells. To explore the targets of miR‚Ä?9a in gastric cancer, bioinformatics analysis was conducted and Robo1 was identified as a putative target of miR‚Ä?9a. Further western blotting and luciferase activity assay data confirmed that miR‚Ä?9a was able to negatively regulate the protein expression of Robo1, through directly binding to the 3'‚Äëuntranslated region of Robo1 mRNA in gastric cancer cells. In addition, it was demonstrated that Robo1 was frequently upregulated in gastric cancer tissues compared with their matched adjacent normal tissues, and a significant inverse correlation was identified between miR‚Ä?9a and Robo1 expression. In addition, knockdown of Robo1 by small interfering RNA markedly inhibited the migratory and invasive capabilities of AGS cells, which the results obtained with overexpression of miR‚Ä?9a. In conclusion, to the best of our knowledge the current study suggested for the first time, that miR‚Ä?9a inhibits migration and invasion in part via direct inhibition of Robo1 in gastric cancer cells. Therefore, Robo1 and miR‚Ä?9a may serve as diagnostic or therapeutic targets for gastric cancer. 

Retracted: No

PubPeer comments:
 Figs 2B, 5C.  The inhibitory effect of miR-29a on the migration and invasion of AGS cells ;  Downregulation of Robo1 by siRNA suppressed migration and invasion in AGS cells .  I set up a spreadsheet to include the various papers using this versatile suite of Transwell images to represent all possible combinations of cell-lines and treatments. This is the 47th manifestation. For comparison: Fig 3 C D from [Zhang et al (2016)] .  Transwell assay were performed to examine the migratory and invasive capacities of Saos-2 and U2OS cells transfected with miR-205 mimic or miR-negative control (NC) mimic , and Fig 7C D,  Transwell assay were performed to examine cell migration and invasion of MG63 or U2OS cells transfected with miR-205 mimic, or co-transfected with miR-205 mimic and RUNX2 plasmid .  Figs 4D, 6D from [Xia et al (2016)] .  Also *[above]* Fig 4C from [Lai, Chen Li (2015)] .  a Transwell assay were performed to examine the cell proliferation of AGS cells transfected with miR-133a mimics, miR-133a inhibitor, or co-transfected with miR-133a mimics and FSCN1 plasmid. Control: AGS cells without any transfection. *[below]* Figs 3(B), 6(B) from [Shi et al (2015)] .  Transwell assay was performed to determine the invasive capacity of the Saos-2 and U-2 OS cells transfected with NC scramble miRNA or miR-204 mimics, respectively. Control, Saos-2 and U-2 OS cells without any transfection ...  Transwell assay was performed to determine the invasive capacity of the Saos-2 and U-2 OS cells transfected with Sirt1 siRNA or co-transfected with miR-204 mimics and the Sirt1 plasmid, respectively. Control, Saos-2 and U-2 OS cells without any transfection .  ,