MicroRNA-138 suppresses neutrophil gelatinase-associated lipocalin expression and inhibits tumorigenicity.
The expression of neutrophil gelatinase-associated lipocalin (NGAL) is up-regulated in some cancers; therefore NGAL has potential as a tumor biomarker. Although the regulation mechanism for this is unknown, one study has shown that it is likely to involve a microRNA (miRNA). Here, we investigate the...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3534095?pdf=render |
| _version_ | 1819123020189401088 |
|---|---|
| author | Ying Chu Lee Woan-Fang Tzeng Tzeon-Jye Chiou Sin Tak Chu |
| author_facet | Ying Chu Lee Woan-Fang Tzeng Tzeon-Jye Chiou Sin Tak Chu |
| author_sort | Ying Chu Lee |
| collection | DOAJ |
| description | The expression of neutrophil gelatinase-associated lipocalin (NGAL) is up-regulated in some cancers; therefore NGAL has potential as a tumor biomarker. Although the regulation mechanism for this is unknown, one study has shown that it is likely to involve a microRNA (miRNA). Here, we investigate the relation between miRNA expression and NGAL expression, and the role of NGAL in tumorigenesis. Using miRNA target-detecting software, we analyze the mRNA sequence of NGAL and identify a target site for microRNA-138 (miR-138) in nucleotides 25-53 of the 3' UTR. We then analyze NGAL and miR-138 expression in three cancer cell lines originating from breast, endometrial and pancreatic carcinomas (the MCF-7, RL95-2 and AsPC-1 cell lines), respectively, using quantitative (real-time) PCR and western blot analysis. Metastasis is a critical event in cancer progression, in which malignant cell proliferation, migration and invasion increase. To determine whether miR-138-regulated NGAL expression is associated with metastasis, the proliferation and migration of the cell line are examined after miR-138 transfection. Using nude mice, we examine both the tumorigenicity of these cell lines and of miR-138-transfected cancer cells in vivo, as well as the effect of treating tumors with an antibody against NGAL. Our results show that these cancer cell lines down-regulate NGAL when miR-138 is highly expressed. Ectopic transfection of miR-138 suppresses NGAL expression and cell migration in RL95-2 and AsPC-1 cells, demonstrating that miR-138-regulated NGAL expression is associated with cell migration. Additionally, injection of the NGAL antibody diminishes NGAL-mediated tumorigenesis in nude mice, and miR-138 transfection of cancer cells reduces tumor formation. As the cell proliferation data showed that the tumor size should be regulated by NGAL-related cell growth. Taken together, our results indicate that NGAL may be a good target for cancer therapy and suggest that miR-138 acts as a tumor suppressor and may prevent metastasis. |
| first_indexed | 2024-12-22T07:01:42Z |
| format | Article |
| id | doaj.art-1a935104723d42089e93340881bf6873 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T07:01:42Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1a935104723d42089e93340881bf68732022-12-21T18:34:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5297910.1371/journal.pone.0052979MicroRNA-138 suppresses neutrophil gelatinase-associated lipocalin expression and inhibits tumorigenicity.Ying Chu LeeWoan-Fang TzengTzeon-Jye ChiouSin Tak ChuThe expression of neutrophil gelatinase-associated lipocalin (NGAL) is up-regulated in some cancers; therefore NGAL has potential as a tumor biomarker. Although the regulation mechanism for this is unknown, one study has shown that it is likely to involve a microRNA (miRNA). Here, we investigate the relation between miRNA expression and NGAL expression, and the role of NGAL in tumorigenesis. Using miRNA target-detecting software, we analyze the mRNA sequence of NGAL and identify a target site for microRNA-138 (miR-138) in nucleotides 25-53 of the 3' UTR. We then analyze NGAL and miR-138 expression in three cancer cell lines originating from breast, endometrial and pancreatic carcinomas (the MCF-7, RL95-2 and AsPC-1 cell lines), respectively, using quantitative (real-time) PCR and western blot analysis. Metastasis is a critical event in cancer progression, in which malignant cell proliferation, migration and invasion increase. To determine whether miR-138-regulated NGAL expression is associated with metastasis, the proliferation and migration of the cell line are examined after miR-138 transfection. Using nude mice, we examine both the tumorigenicity of these cell lines and of miR-138-transfected cancer cells in vivo, as well as the effect of treating tumors with an antibody against NGAL. Our results show that these cancer cell lines down-regulate NGAL when miR-138 is highly expressed. Ectopic transfection of miR-138 suppresses NGAL expression and cell migration in RL95-2 and AsPC-1 cells, demonstrating that miR-138-regulated NGAL expression is associated with cell migration. Additionally, injection of the NGAL antibody diminishes NGAL-mediated tumorigenesis in nude mice, and miR-138 transfection of cancer cells reduces tumor formation. As the cell proliferation data showed that the tumor size should be regulated by NGAL-related cell growth. Taken together, our results indicate that NGAL may be a good target for cancer therapy and suggest that miR-138 acts as a tumor suppressor and may prevent metastasis.http://europepmc.org/articles/PMC3534095?pdf=render |
| spellingShingle | Ying Chu Lee Woan-Fang Tzeng Tzeon-Jye Chiou Sin Tak Chu MicroRNA-138 suppresses neutrophil gelatinase-associated lipocalin expression and inhibits tumorigenicity. PLoS ONE |
| title | MicroRNA-138 suppresses neutrophil gelatinase-associated lipocalin expression and inhibits tumorigenicity. |
| title_full | MicroRNA-138 suppresses neutrophil gelatinase-associated lipocalin expression and inhibits tumorigenicity. |
| title_fullStr | MicroRNA-138 suppresses neutrophil gelatinase-associated lipocalin expression and inhibits tumorigenicity. |
| title_full_unstemmed | MicroRNA-138 suppresses neutrophil gelatinase-associated lipocalin expression and inhibits tumorigenicity. |
| title_short | MicroRNA-138 suppresses neutrophil gelatinase-associated lipocalin expression and inhibits tumorigenicity. |
| title_sort | microrna 138 suppresses neutrophil gelatinase associated lipocalin expression and inhibits tumorigenicity |
| url | http://europepmc.org/articles/PMC3534095?pdf=render |
| work_keys_str_mv | AT yingchulee microrna138suppressesneutrophilgelatinaseassociatedlipocalinexpressionandinhibitstumorigenicity AT woanfangtzeng microrna138suppressesneutrophilgelatinaseassociatedlipocalinexpressionandinhibitstumorigenicity AT tzeonjyechiou microrna138suppressesneutrophilgelatinaseassociatedlipocalinexpressionandinhibitstumorigenicity AT sintakchu microrna138suppressesneutrophilgelatinaseassociatedlipocalinexpressionandinhibitstumorigenicity |