Loss of tumor suppressor miR-126 contributes to the development of hepatitis B virus–related hepatocellular carcinoma metastasis through the upregulation of ADAM9
Hepatocellular carcinoma is the most common histological type of primary liver cancer, which represents the second leading cause of cancer-related mortality. MiR-126 was reported to be downregulated in hepatocellular carcinoma tissues, compared with its levels in noncancerous tissues. However, basel...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2017-06-01
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| Series: | Tumor Biology |
| Online Access: | https://doi.org/10.1177/1010428317709128 |
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| author | Le-yang Xiang Huo-hui Ou Xin-cheng Liu Zhan-jun Chen Xiang-hong Li Yu Huang Ding-hua Yang |
| author_facet | Le-yang Xiang Huo-hui Ou Xin-cheng Liu Zhan-jun Chen Xiang-hong Li Yu Huang Ding-hua Yang |
| author_sort | Le-yang Xiang |
| collection | DOAJ |
| description | Hepatocellular carcinoma is the most common histological type of primary liver cancer, which represents the second leading cause of cancer-related mortality. MiR-126 was reported to be downregulated in hepatocellular carcinoma tissues, compared with its levels in noncancerous tissues. However, baseline miR-126 expression levels in hepatitis B virus–related hepatocellular carcinoma patients who did not undergo pre-operational treatment remains unknown since hepatitis B virus infection and pre-operational transcatheter arterial chemoembolization were shown to upregulate miR-126 expression. Here, we demonstrated that miR-126 is generally downregulated in a homogeneous population of pre-operational treatment–naïve hepatitis B virus–related hepatocellular carcinoma patients (84.0%, 84/100), and its expression is significantly associated with pre-operational alpha-fetoprotein levels ( p < 0.05), microvascular invasion ( p < 0.05), tumor metastasis ( p < 0.05), as well as early recurrence (12 months after surgery; p < 0.01). Furthermore, the results of our study revealed that miR-126 is negatively correlated with ADAM9 expression in hepatitis B virus–related hepatocellular carcinoma patients. Overexpression of miR-126 was shown to attenuate ADAM9 expression in hepatocellular carcinoma cells, which subsequently inhibits cell migration and invasion in vitro. In addition, Cox proportional hazards regression model analysis showed that ADAM9 levels, tumor number, microvascular invasion, and tumor metastasis rate represent independent prognostic factors for shorter recurrence-free survival. In conclusion, we demonstrated that the loss of tumor suppressor miR-126 in hepatitis B virus–related hepatocellular carcinoma cells contributes to the development of metastases through the upregulated expression of its target gene, ADAM9. MiR-126-ADAM9 pathway–based therapeutic targeting may represent a novel approach for the inhibition of hepatitis B virus–related hepatocellular carcinoma metastases. |
| format | Article |
| id | doaj-art-2e30494732fc40b8885c59771b2da3ed |
| institution | Kabale University |
| issn | 1423-0380 |
| language | English |
| publishDate | 2017-06-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Tumor Biology |
| spelling | doaj-art-2e30494732fc40b8885c59771b2da3ed2025-08-20T03:33:10ZengSAGE PublishingTumor Biology1423-03802017-06-013910.1177/1010428317709128Loss of tumor suppressor miR-126 contributes to the development of hepatitis B virus–related hepatocellular carcinoma metastasis through the upregulation of ADAM9Le-yang Xiang0Huo-hui Ou1Xin-cheng Liu2Zhan-jun Chen3Xiang-hong Li4Yu Huang5Ding-hua Yang6Department of Hepatobiliary Surgery, Nanfang Hospital Affiliated to Southern Medical University, Guangzhou, ChinaDepartment of Hepatobiliary Surgery, Nanfang Hospital Affiliated to Southern Medical University, Guangzhou, ChinaDepartment of Urology Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, ChinaDepartment of Hepatobiliary Surgery, Nanfang Hospital Affiliated to Southern Medical University, Guangzhou, ChinaDepartment of Hepatobiliary Surgery, Nanfang Hospital Affiliated to Southern Medical University, Guangzhou, ChinaDepartment of Laboratory Medicine, Nanfang Hospital Affiliated to Southern Medical University, Guangzhou, ChinaDepartment of Hepatobiliary Surgery, Nanfang Hospital Affiliated to Southern Medical University, Guangzhou, ChinaHepatocellular carcinoma is the most common histological type of primary liver cancer, which represents the second leading cause of cancer-related mortality. MiR-126 was reported to be downregulated in hepatocellular carcinoma tissues, compared with its levels in noncancerous tissues. However, baseline miR-126 expression levels in hepatitis B virus–related hepatocellular carcinoma patients who did not undergo pre-operational treatment remains unknown since hepatitis B virus infection and pre-operational transcatheter arterial chemoembolization were shown to upregulate miR-126 expression. Here, we demonstrated that miR-126 is generally downregulated in a homogeneous population of pre-operational treatment–naïve hepatitis B virus–related hepatocellular carcinoma patients (84.0%, 84/100), and its expression is significantly associated with pre-operational alpha-fetoprotein levels ( p < 0.05), microvascular invasion ( p < 0.05), tumor metastasis ( p < 0.05), as well as early recurrence (12 months after surgery; p < 0.01). Furthermore, the results of our study revealed that miR-126 is negatively correlated with ADAM9 expression in hepatitis B virus–related hepatocellular carcinoma patients. Overexpression of miR-126 was shown to attenuate ADAM9 expression in hepatocellular carcinoma cells, which subsequently inhibits cell migration and invasion in vitro. In addition, Cox proportional hazards regression model analysis showed that ADAM9 levels, tumor number, microvascular invasion, and tumor metastasis rate represent independent prognostic factors for shorter recurrence-free survival. In conclusion, we demonstrated that the loss of tumor suppressor miR-126 in hepatitis B virus–related hepatocellular carcinoma cells contributes to the development of metastases through the upregulated expression of its target gene, ADAM9. MiR-126-ADAM9 pathway–based therapeutic targeting may represent a novel approach for the inhibition of hepatitis B virus–related hepatocellular carcinoma metastases.https://doi.org/10.1177/1010428317709128 |
| spellingShingle | Le-yang Xiang Huo-hui Ou Xin-cheng Liu Zhan-jun Chen Xiang-hong Li Yu Huang Ding-hua Yang Loss of tumor suppressor miR-126 contributes to the development of hepatitis B virus–related hepatocellular carcinoma metastasis through the upregulation of ADAM9 Tumor Biology |
| title | Loss of tumor suppressor miR-126 contributes to the development of hepatitis B virus–related hepatocellular carcinoma metastasis through the upregulation of ADAM9 |
| title_full | Loss of tumor suppressor miR-126 contributes to the development of hepatitis B virus–related hepatocellular carcinoma metastasis through the upregulation of ADAM9 |
| title_fullStr | Loss of tumor suppressor miR-126 contributes to the development of hepatitis B virus–related hepatocellular carcinoma metastasis through the upregulation of ADAM9 |
| title_full_unstemmed | Loss of tumor suppressor miR-126 contributes to the development of hepatitis B virus–related hepatocellular carcinoma metastasis through the upregulation of ADAM9 |
| title_short | Loss of tumor suppressor miR-126 contributes to the development of hepatitis B virus–related hepatocellular carcinoma metastasis through the upregulation of ADAM9 |
| title_sort | loss of tumor suppressor mir 126 contributes to the development of hepatitis b virus related hepatocellular carcinoma metastasis through the upregulation of adam9 |
| url | https://doi.org/10.1177/1010428317709128 |
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