Deregulated microRNAs in gastric cancer tissue-derived mesenchymal stem cells: novel biomarkers and a mechanism for gastric cancer.
BACKGROUND
MicroRNAs (miRNAs) are involved in gastric cancer development and progression. However, the expression and role of miRNAs in gastric cancer stromal cells are still unclear.


METHODS
The miRNAs differentially expressed in gastric cancer tissue-derived mesenchymal stem cells (GC-MSCs) relative to adjacent non-cancerous tissue-derived MSCs (GCN-MSCs) and in cancer tissues relative to adjacent non-cancerous tissues were screened using miRNA microarray and validated by quantitative RT-PCR. The impact of GC-MSCs on HGC-27 cells was observed in vitro using colony formation and transwell assays, and these cells were subcutaneously co-injected into mice to assess tumour growth in vivo. Exogenous downregulation of miR-221 expression in cells was achieved using an miRNA inhibitor.


RESULTS
miR-214, miR-221 and miR-222 were found to be commonly upregulated in GC-MSCs and cancer tissues. Their levels were tightly associated with lymph node metastasis, venous invasion and the TNM stage. Gastric cancer tissue-derived mesenchymal stem cells significantly promoted HGC-27 growth and migration and increased the expression of miR-221 via paracrine secretion, and the targeted inhibition of miR-221 in GC-MSCs could block its tumour-supporting role. GC-MSC-derived exosomes were found to deliver miR-221 to HGC-27 cells and promoted their proliferation and migration.


CONCLUSIONS
Gastric cancer tissue-derived mesenchymal stem cells favour gastric cancer progression by transferring exosomal miRNAs to gastric cancer cells, thus providing a novel mechanism for the role of GC-MSCs and new biomarkers for gastric cancer.
School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, China.
M
M
Wang
School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, China.
C
C
Zhao
School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, China.
H
H
Shi
School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, China.
B
B
Zhang
School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, China.
L
L
Zhang
School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, China.
X
X
Zhang
Department of Surgery, The First People's Hospital of Zhenjiang, Zhenjiang 212001, Jiangsu, China.
S
S
Wang
School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, China.
X
X
Wu
School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, China.
T
T
Yang
School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, China.
F
F
Huang
School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, China.
J
J
Cai
School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, China.
Q
Q
Zhu
School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, China.
W
W
Zhu
School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, China.
H
H
Qian
School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, China.
W
W
Xu
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation; D055354:Exosomes / Q000235:genetics / Q000473:pathology; D006801:Humans; D008207:Lymphatic Metastasis; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D019899:Paracrine Communication / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D035683:MicroRNAs