Hypermethylation of miR-338-3p and Impact of its Suppression on Cell Metastasis Through N-Cadherin Accumulation at the Cell -Cell Junction and Degradation of MMP in Gastric Cancer
Background/Aims: MicroRNAs (miRNAs) have been well studied in human carcinogenesis and cancer progression. Our previous study showed the down-regulation of miR-338-3p expression in human gastric cancer (GC). However, the reasons of this dysregulation remain largely unclear. Methods: Bisulfite sequen...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2018-10-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | https://www.karger.com/Article/FullText/494153 |
| _version_ | 1819111561984212992 |
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| author | Bo Guo Jing Zhang Qian Li Zhenghao Zhao Wenjing Wang Kaiyue Zhou Xiaofei Wang Dongdong Tong Lingyu Zhao Juan Yang Chen Huang |
| author_facet | Bo Guo Jing Zhang Qian Li Zhenghao Zhao Wenjing Wang Kaiyue Zhou Xiaofei Wang Dongdong Tong Lingyu Zhao Juan Yang Chen Huang |
| author_sort | Bo Guo |
| collection | DOAJ |
| description | Background/Aims: MicroRNAs (miRNAs) have been well studied in human carcinogenesis and cancer progression. Our previous study showed the down-regulation of miR-338-3p expression in human gastric cancer (GC). However, the reasons of this dysregulation remain largely unclear. Methods: Bisulfite sequence analysis was performed to explore the methylation status of the promoter region of miR-338-3p. Cell wound-healing and transwell assays were performed to examine the capacity of cell migration and cell interaction. A dual-luciferase reporter was used to validate the bioinformatics-predicted target gene of miR-338-3p. Western blotting, RNA interference, and immunofluorescence (IF) were used to evaluate the expression of MMPs and the location of N-cadherin to determine the mechanism underlying miR-338-3p-induced anti-tumor effects. Results: miR-338-3p was epigenetically silenced, and this loss of expression was significantly correlated with the Borrmann Stage in GC. Restoring miR-338-3p expression in BGC-823 cells inhibited cell migration and invasion. Moreover, Ras-related protein (Rab-14) and Hedgehog acyltransferase (Hhat) were identified as direct targets of miR-338-3p. Both enforced expression of miR-338-3p and small interfering RNA induced Rab14-mediated accumulation of N-cadherin in the cell -cell junctions or Hhat-associated matrix metalloproteinase (MMP) degradation, which may underline the metastasis defects caused by loss of miR-338-3p in GC. Conclusion: These data indicate that miR-338-3p functions as a tumor suppressor in GC, and that the hypermethylation status of its CpG island might be a novel potential strategy for treating GC. |
| first_indexed | 2024-12-22T03:59:35Z |
| format | Article |
| id | doaj.art-188f3731e6b14f7b9f0cf5b2fcb7e442 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-22T03:59:35Z |
| publishDate | 2018-10-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-188f3731e6b14f7b9f0cf5b2fcb7e4422022-12-21T18:39:47ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-10-0150241142510.1159/000494153494153Hypermethylation of miR-338-3p and Impact of its Suppression on Cell Metastasis Through N-Cadherin Accumulation at the Cell -Cell Junction and Degradation of MMP in Gastric CancerBo GuoJing ZhangQian LiZhenghao ZhaoWenjing WangKaiyue ZhouXiaofei WangDongdong TongLingyu ZhaoJuan YangChen HuangBackground/Aims: MicroRNAs (miRNAs) have been well studied in human carcinogenesis and cancer progression. Our previous study showed the down-regulation of miR-338-3p expression in human gastric cancer (GC). However, the reasons of this dysregulation remain largely unclear. Methods: Bisulfite sequence analysis was performed to explore the methylation status of the promoter region of miR-338-3p. Cell wound-healing and transwell assays were performed to examine the capacity of cell migration and cell interaction. A dual-luciferase reporter was used to validate the bioinformatics-predicted target gene of miR-338-3p. Western blotting, RNA interference, and immunofluorescence (IF) were used to evaluate the expression of MMPs and the location of N-cadherin to determine the mechanism underlying miR-338-3p-induced anti-tumor effects. Results: miR-338-3p was epigenetically silenced, and this loss of expression was significantly correlated with the Borrmann Stage in GC. Restoring miR-338-3p expression in BGC-823 cells inhibited cell migration and invasion. Moreover, Ras-related protein (Rab-14) and Hedgehog acyltransferase (Hhat) were identified as direct targets of miR-338-3p. Both enforced expression of miR-338-3p and small interfering RNA induced Rab14-mediated accumulation of N-cadherin in the cell -cell junctions or Hhat-associated matrix metalloproteinase (MMP) degradation, which may underline the metastasis defects caused by loss of miR-338-3p in GC. Conclusion: These data indicate that miR-338-3p functions as a tumor suppressor in GC, and that the hypermethylation status of its CpG island might be a novel potential strategy for treating GC.https://www.karger.com/Article/FullText/494153miR-338-3pGastric cancerMetastasisRab14-N-cadherinHhat-MMP signaling |
| spellingShingle | Bo Guo Jing Zhang Qian Li Zhenghao Zhao Wenjing Wang Kaiyue Zhou Xiaofei Wang Dongdong Tong Lingyu Zhao Juan Yang Chen Huang Hypermethylation of miR-338-3p and Impact of its Suppression on Cell Metastasis Through N-Cadherin Accumulation at the Cell -Cell Junction and Degradation of MMP in Gastric Cancer Cellular Physiology and Biochemistry miR-338-3p Gastric cancer Metastasis Rab14-N-cadherin Hhat-MMP signaling |
| title | Hypermethylation of miR-338-3p and Impact of its Suppression on Cell Metastasis Through N-Cadherin Accumulation at the Cell -Cell Junction and Degradation of MMP in Gastric Cancer |
| title_full | Hypermethylation of miR-338-3p and Impact of its Suppression on Cell Metastasis Through N-Cadherin Accumulation at the Cell -Cell Junction and Degradation of MMP in Gastric Cancer |
| title_fullStr | Hypermethylation of miR-338-3p and Impact of its Suppression on Cell Metastasis Through N-Cadherin Accumulation at the Cell -Cell Junction and Degradation of MMP in Gastric Cancer |
| title_full_unstemmed | Hypermethylation of miR-338-3p and Impact of its Suppression on Cell Metastasis Through N-Cadherin Accumulation at the Cell -Cell Junction and Degradation of MMP in Gastric Cancer |
| title_short | Hypermethylation of miR-338-3p and Impact of its Suppression on Cell Metastasis Through N-Cadherin Accumulation at the Cell -Cell Junction and Degradation of MMP in Gastric Cancer |
| title_sort | hypermethylation of mir 338 3p and impact of its suppression on cell metastasis through n cadherin accumulation at the cell cell junction and degradation of mmp in gastric cancer |
| topic | miR-338-3p Gastric cancer Metastasis Rab14-N-cadherin Hhat-MMP signaling |
| url | https://www.karger.com/Article/FullText/494153 |
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