ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis
Abstract Background Pancreatic cancer is a highly lethal malignancy with poor prognosis. Anillin (ANLN), an actin binding protein, is upregulated and plays an important role in many malignant tumors. However, the precise role of ANLN in pancreatic cancer remains unclear. Methods The expression of AN...
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doaj-22a7790181d2493e93c323c59069765c2020-11-25T03:35:53ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662019-08-0138112010.1186/s13046-019-1340-7ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axisAnbin Wang0Haisu Dai1Yi Gong2Chengcheng Zhang3Junjie Shu4Yuandeng Luo5Yan Jiang6Wei Liu7Ping Bie8Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University)Abstract Background Pancreatic cancer is a highly lethal malignancy with poor prognosis. Anillin (ANLN), an actin binding protein, is upregulated and plays an important role in many malignant tumors. However, the precise role of ANLN in pancreatic cancer remains unclear. Methods The expression of ANLN and its association with pancreatic cancer patient survival were analyzed using an online database and confirmed by immunohistochemistry. The ANLN protein expression in pancreatic cancer cell lines was detected by Western blot. Cell proliferation, colony formation and transwell assays in vitro and in vivo tumor growth were used to determine the role of ANLN in pancreatic cancer. Gene expression microarray analysis and a series of in vitro assays were used to elucidate the mechanisms of ANLN regulating pancreatic cancer progression. Results We found that the ANLN expression was significantly upregulated in pancreatic cancer tissues and cell lines. The high expression of ANLN was associated with tumor size, tumor differentiation, TNM stage, lymph node metastasis, distant metastasis and poor prognosis in pancreatic cancer. ANLN downregulation significantly inhibited cell proliferation, colony formation, migration, invasion and tumorigenicity in nude mice. Meanwhile, we found that ANLN knockdown inhibited several cell-cell adhesion related genes, including the gene encoding LIM and SH3 protein 1 (LASP1). LASP1 upregulation partially reversed the tumor-suppressive effect of ANLN downregulation on pancreatic cancer cell progression. Moreover, we found that ANLN downregulation induced the expression of miR-218-5p which inhibited LASP1 expression through binding to its 3’UTR. We also found that ANLN-induced enhancer of zeste homolog 2 (EZH2) upregulation was involved in regulating miR-218-5p/LASP1 signaling axis. EZH2 upregulation or miR-218-5p downregulation partially reversed the tumor-suppressive effect of ANLN downregulation on pancreatic cancer cell progression. Conclusion ANLN contributed to pancreatic cancer progression by regulating EZH2/miR-218-5p/LASP1 signaling axis. These findings suggest that ANLN may be a candidate therapeutic target in pancreatic cancer.http://link.springer.com/article/10.1186/s13046-019-1340-7Pancreatic cancerANLNEZH2miR-218-5pLASP1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anbin Wang Haisu Dai Yi Gong Chengcheng Zhang Junjie Shu Yuandeng Luo Yan Jiang Wei Liu Ping Bie |
spellingShingle |
Anbin Wang Haisu Dai Yi Gong Chengcheng Zhang Junjie Shu Yuandeng Luo Yan Jiang Wei Liu Ping Bie ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis Journal of Experimental & Clinical Cancer Research Pancreatic cancer ANLN EZH2 miR-218-5p LASP1 |
author_facet |
Anbin Wang Haisu Dai Yi Gong Chengcheng Zhang Junjie Shu Yuandeng Luo Yan Jiang Wei Liu Ping Bie |
author_sort |
Anbin Wang |
title |
ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis |
title_short |
ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis |
title_full |
ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis |
title_fullStr |
ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis |
title_full_unstemmed |
ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis |
title_sort |
anln-induced ezh2 upregulation promotes pancreatic cancer progression by mediating mir-218-5p/lasp1 signaling axis |
publisher |
BMC |
series |
Journal of Experimental & Clinical Cancer Research |
issn |
1756-9966 |
publishDate |
2019-08-01 |
description |
Abstract Background Pancreatic cancer is a highly lethal malignancy with poor prognosis. Anillin (ANLN), an actin binding protein, is upregulated and plays an important role in many malignant tumors. However, the precise role of ANLN in pancreatic cancer remains unclear. Methods The expression of ANLN and its association with pancreatic cancer patient survival were analyzed using an online database and confirmed by immunohistochemistry. The ANLN protein expression in pancreatic cancer cell lines was detected by Western blot. Cell proliferation, colony formation and transwell assays in vitro and in vivo tumor growth were used to determine the role of ANLN in pancreatic cancer. Gene expression microarray analysis and a series of in vitro assays were used to elucidate the mechanisms of ANLN regulating pancreatic cancer progression. Results We found that the ANLN expression was significantly upregulated in pancreatic cancer tissues and cell lines. The high expression of ANLN was associated with tumor size, tumor differentiation, TNM stage, lymph node metastasis, distant metastasis and poor prognosis in pancreatic cancer. ANLN downregulation significantly inhibited cell proliferation, colony formation, migration, invasion and tumorigenicity in nude mice. Meanwhile, we found that ANLN knockdown inhibited several cell-cell adhesion related genes, including the gene encoding LIM and SH3 protein 1 (LASP1). LASP1 upregulation partially reversed the tumor-suppressive effect of ANLN downregulation on pancreatic cancer cell progression. Moreover, we found that ANLN downregulation induced the expression of miR-218-5p which inhibited LASP1 expression through binding to its 3’UTR. We also found that ANLN-induced enhancer of zeste homolog 2 (EZH2) upregulation was involved in regulating miR-218-5p/LASP1 signaling axis. EZH2 upregulation or miR-218-5p downregulation partially reversed the tumor-suppressive effect of ANLN downregulation on pancreatic cancer cell progression. Conclusion ANLN contributed to pancreatic cancer progression by regulating EZH2/miR-218-5p/LASP1 signaling axis. These findings suggest that ANLN may be a candidate therapeutic target in pancreatic cancer. |
topic |
Pancreatic cancer ANLN EZH2 miR-218-5p LASP1 |
url |
http://link.springer.com/article/10.1186/s13046-019-1340-7 |
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