HMMR promotes invasion and metastasis of hepatocellular carcinoma via activating MEK/ERK signaling pathway
Objective To investigate the effect of hyaluronan-mediated motility receptor (HMMR) on the invasion and metastasis of hepatocellular carcinoma (HCC) cells. Methods The expression levels of HMMR in HCC cell lines and tissues were detected by qRT-PCR, Western blotting and immunohistochemical assay. T...
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Editorial Office of Journal of Army Medical University
2022-09-01
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| Series: | 陆军军医大学学报 |
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| Online Access: | http://aammt.tmmu.edu.cn/Upload/rhtml/202203004.htm |
| _version_ | 1798003393476689920 |
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| author | LI Xun YAN Jiao CAI Shunli CHEN Huajian |
| author_facet | LI Xun YAN Jiao CAI Shunli CHEN Huajian |
| author_sort | LI Xun |
| collection | DOAJ |
| description | Objective To investigate the effect of hyaluronan-mediated motility receptor (HMMR) on the invasion and metastasis of hepatocellular carcinoma (HCC) cells. Methods The expression levels of HMMR in HCC cell lines and tissues were detected by qRT-PCR, Western blotting and immunohistochemical assay. The effects of silencing/overexpression of HMMR on the migration and invasion of HCC cells were observed by wound healing test and Transwell assay. Control HMMR cells and shRNA targeting HMMR cells were respectively injected into nude mice via tail vein to construct a mouse model of lung metastasis. Western blotting was used to detect the effect of HMMR expression on the protein levels of E-cadherin, N-cadherin, Vimentin, p-MEK and p-ERK. Results HMMR was highly expressed in liver cancer cell lines, and was generally up-regulated in HCC tissues than adjacent normal tissues (P < 0.05), and the mRNA and protein levels of HMMR were significantly higher in the metastatic HCC tissues than the non-metastatic HCC tissues (P < 0.05). Silencing HMMR weakened the migration and invasion abilities of cells (P < 0.01), down-regulated E-cadherin protein level and up-regulated N-cadherin and Vimentin levels (P < 0.01). While overexpression of HMMR promoted the motility and migration and invasion abilities of HCC cells (P < 0.01), enhanced the expression of N-cadherin and Vimentin, and down-regulated the level of E-cadherin (P < 0.01). In vivo study showed that knockdown of HMMR resulted in significantly less lung metastases than the control group (P < 0.05), while, overexpression of HMMR enhanced the levels of p-MEK and p-ERK (P < 0.01), but had no effect on MEK and ERK levels (P>0.05). Furthermore, MEK inhibitor U1026 significantly reduced the migration and invasion abilities of HMMR-overexpressed Huh7 cells (P < 0.01). Conclusion HMMR is highly expressed in HCC cells, and may promote the migration and invasion of HCC cells via MEK/ERK signaling pathway.
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| first_indexed | 2024-04-11T12:06:51Z |
| format | Article |
| id | doaj.art-fa69e557ba534754ade557eb2a0a90f4 |
| institution | Directory Open Access Journal |
| issn | 2097-0927 |
| language | zho |
| last_indexed | 2024-04-11T12:06:51Z |
| publishDate | 2022-09-01 |
| publisher | Editorial Office of Journal of Army Medical University |
| record_format | Article |
| series | 陆军军医大学学报 |
| spelling | doaj.art-fa69e557ba534754ade557eb2a0a90f42022-12-22T04:24:42ZzhoEditorial Office of Journal of Army Medical University陆军军医大学学报2097-09272022-09-0144171720172710.16016/j.2097-0927.202203004HMMR promotes invasion and metastasis of hepatocellular carcinoma via activating MEK/ERK signaling pathwayLI Xun0YAN Jiao1CAI Shunli2 CHEN Huajian3Department of Clinical Laboratory, Chongqing Emergency Medical Center, Chongqing, 400016, ChinaDepartment of Hepatobiliary Surgery, Chongqing Emergency Medical Center, Chongqing, 400016, ChinaDepartment of Clinical Laboratory, Chongqing Emergency Medical Center, Chongqing, 400016, ChinaDepartment of Clinical Laboratory, Chongqing Emergency Medical Center, Chongqing, 400016, China Objective To investigate the effect of hyaluronan-mediated motility receptor (HMMR) on the invasion and metastasis of hepatocellular carcinoma (HCC) cells. Methods The expression levels of HMMR in HCC cell lines and tissues were detected by qRT-PCR, Western blotting and immunohistochemical assay. The effects of silencing/overexpression of HMMR on the migration and invasion of HCC cells were observed by wound healing test and Transwell assay. Control HMMR cells and shRNA targeting HMMR cells were respectively injected into nude mice via tail vein to construct a mouse model of lung metastasis. Western blotting was used to detect the effect of HMMR expression on the protein levels of E-cadherin, N-cadherin, Vimentin, p-MEK and p-ERK. Results HMMR was highly expressed in liver cancer cell lines, and was generally up-regulated in HCC tissues than adjacent normal tissues (P < 0.05), and the mRNA and protein levels of HMMR were significantly higher in the metastatic HCC tissues than the non-metastatic HCC tissues (P < 0.05). Silencing HMMR weakened the migration and invasion abilities of cells (P < 0.01), down-regulated E-cadherin protein level and up-regulated N-cadherin and Vimentin levels (P < 0.01). While overexpression of HMMR promoted the motility and migration and invasion abilities of HCC cells (P < 0.01), enhanced the expression of N-cadherin and Vimentin, and down-regulated the level of E-cadherin (P < 0.01). In vivo study showed that knockdown of HMMR resulted in significantly less lung metastases than the control group (P < 0.05), while, overexpression of HMMR enhanced the levels of p-MEK and p-ERK (P < 0.01), but had no effect on MEK and ERK levels (P>0.05). Furthermore, MEK inhibitor U1026 significantly reduced the migration and invasion abilities of HMMR-overexpressed Huh7 cells (P < 0.01). Conclusion HMMR is highly expressed in HCC cells, and may promote the migration and invasion of HCC cells via MEK/ERK signaling pathway. http://aammt.tmmu.edu.cn/Upload/rhtml/202203004.htmhepatocellular carcinomahyaluronan-mediated motility receptorepithelial-mesenchymal transitionmetastasismek/erk signaling pathway |
| spellingShingle | LI Xun YAN Jiao CAI Shunli CHEN Huajian HMMR promotes invasion and metastasis of hepatocellular carcinoma via activating MEK/ERK signaling pathway 陆军军医大学学报 hepatocellular carcinoma hyaluronan-mediated motility receptor epithelial-mesenchymal transition metastasis mek/erk signaling pathway |
| title | HMMR promotes invasion and metastasis of hepatocellular carcinoma via activating MEK/ERK signaling pathway |
| title_full | HMMR promotes invasion and metastasis of hepatocellular carcinoma via activating MEK/ERK signaling pathway |
| title_fullStr | HMMR promotes invasion and metastasis of hepatocellular carcinoma via activating MEK/ERK signaling pathway |
| title_full_unstemmed | HMMR promotes invasion and metastasis of hepatocellular carcinoma via activating MEK/ERK signaling pathway |
| title_short | HMMR promotes invasion and metastasis of hepatocellular carcinoma via activating MEK/ERK signaling pathway |
| title_sort | hmmr promotes invasion and metastasis of hepatocellular carcinoma via activating mek erk signaling pathway |
| topic | hepatocellular carcinoma hyaluronan-mediated motility receptor epithelial-mesenchymal transition metastasis mek/erk signaling pathway |
| url | http://aammt.tmmu.edu.cn/Upload/rhtml/202203004.htm |
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