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MiR-136 inhibits gastric cancer-specific peritoneal metastasis by targeting HOXC10.

Abstract Functions of microRNAs have been characterized in the embryologic, physiologic, and oncogenic processes, but the role of microRNAs in mediating tumor-specific organ metastasis was addressed only recently and still absent in gastric cancer peritoneal metastasis. Here, we used the microarray analysis to define the gastric cancer peritoneal metastasis-related microRNAs from highly peritoneal metastatic derivatives (GC-9811P cells) and the parental GC-9811 human gastric cancer cells. MiR-136 was found to be decreased in all peritoneal metastatic sublines when compared with that in the parental line. We further confirmed that miR-136 expression is frequently downregulated in gastric cancer peritoneal metastasis cells and tissues and its low expression is significantly associated with more peritoneal metastasis and worse prognosis. Moreover, restoring the expression of miR-136 could inhibit gastric cancer peritoneal metastasis in vitro and in vivo. Subsequent investigation characterized HOXC10 as a direct target of miR-136. In addition, knockdown of HOXC10 reduced GC-9811P cell migration and invasion, similar to the phenotype observed with miR-136 restoration in these cells, indicating that HOXC10 functions as a metastasis promoter in gastric cancer peritoneal metastasis. Upregulation of HOXC10 in parental GC-9811 cells resulted in a dramatic reduction of in vitro migration, invasion, and in vivo peritoneal metastasis. Furthermore, our results showed that ectopic expression of HOXC10 could reverse inhibition of metastasis by overexpressed miR-136 in GC-9811P cells. Our findings provide new insights into the role of miR-136 in the gastric cancer-specific peritoneal metastasis and implicate the potential application of miR-136 in gastric cancer peritoneal metastasis therapy.
PMID
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Authors

Mayor MeshTerms
Keywords

HOXC10

MiR-136

gastric cancer

peritoneal metastasis

prognosis

Journal Title tumour biology : the journal of the international society for oncodevelopmental biology and medicine
Publication Year Start




PMID- 28656883
OWN - NLM
STAT- MEDLINE
DA  - 20170628
DCOM- 20170711
LR  - 20170713
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 39
IP  - 6
DP  - 2017 Jun
TI  - MiR-136 inhibits gastric cancer-specific peritoneal metastasis by targeting
      HOXC10.
PG  - 1010428317706207
LID - 10.1177/1010428317706207 [doi]
AB  - Functions of microRNAs have been characterized in the embryologic, physiologic,
      and oncogenic processes, but the role of microRNAs in mediating tumor-specific
      organ metastasis was addressed only recently and still absent in gastric cancer
      peritoneal metastasis. Here, we used the microarray analysis to define the
      gastric cancer peritoneal metastasis-related microRNAs from highly peritoneal
      metastatic derivatives (GC-9811P cells) and the parental GC-9811 human gastric
      cancer cells. MiR-136 was found to be decreased in all peritoneal metastatic
      sublines when compared with that in the parental line. We further confirmed that 
      miR-136 expression is frequently downregulated in gastric cancer peritoneal
      metastasis cells and tissues and its low expression is significantly associated
      with more peritoneal metastasis and worse prognosis. Moreover, restoring the
      expression of miR-136 could inhibit gastric cancer peritoneal metastasis in vitro
      and in vivo. Subsequent investigation characterized HOXC10 as a direct target of 
      miR-136. In addition, knockdown of HOXC10 reduced GC-9811P cell migration and
      invasion, similar to the phenotype observed with miR-136 restoration in these
      cells, indicating that HOXC10 functions as a metastasis promoter in gastric
      cancer peritoneal metastasis. Upregulation of HOXC10 in parental GC-9811 cells
      resulted in a dramatic reduction of in vitro migration, invasion, and in vivo
      peritoneal metastasis. Furthermore, our results showed that ectopic expression of
      HOXC10 could reverse inhibition of metastasis by overexpressed miR-136 in
      GC-9811P cells. Our findings provide new insights into the role of miR-136 in the
      gastric cancer-specific peritoneal metastasis and implicate the potential
      application of miR-136 in gastric cancer peritoneal metastasis therapy.
FAU - Zheng, Jianyong
AU  - Zheng J
AD  - 1 State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases,
      The Fourth Military Medical University, Xi'an, China.
FAU - Ge, Peng
AU  - Ge P
AD  - 1 State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases,
      The Fourth Military Medical University, Xi'an, China.
AD  - 2 Xi'an Central Hospital, Xi'an, China.
FAU - Liu, Xiaonan
AU  - Liu X
AD  - 1 State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases,
      The Fourth Military Medical University, Xi'an, China.
FAU - Wei, Jiangpeng
AU  - Wei J
AD  - 1 State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases,
      The Fourth Military Medical University, Xi'an, China.
FAU - Wu, Guosheng
AU  - Wu G
AD  - 1 State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases,
      The Fourth Military Medical University, Xi'an, China.
FAU - Li, Xiaohua
AU  - Li X
AD  - 1 State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases,
      The Fourth Military Medical University, Xi'an, China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental
      Biology and Medicine
JID - 8409922
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (HOXC10 protein, human)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (MIRN136 microRNA, human)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Animals
MH  - Biomarkers, Tumor/biosynthesis/*genetics
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Homeodomain Proteins/*biosynthesis/genetics
MH  - Humans
MH  - Mice
MH  - MicroRNAs/*genetics
MH  - Peritoneal Neoplasms/*genetics/pathology/secondary
MH  - Peritoneum/pathology
MH  - Promoter Regions, Genetic
MH  - Stomach Neoplasms/*genetics/pathology
MH  - Xenograft Model Antitumor Assays
OTO - NOTNLM
OT  - HOXC10
OT  - MiR-136
OT  - gastric cancer
OT  - peritoneal metastasis
OT  - prognosis
EDAT- 2017/06/29 06:00
MHDA- 2017/07/14 06:00
CRDT- 2017/06/29 06:00
AID - 10.1177/1010428317706207 [doi]
PST - ppublish
SO  - Tumour Biol. 2017 Jun;39(6):1010428317706207. doi: 10.1177/1010428317706207.