MiR-145 Regulates the Chemoresistance of Hepatic Carcinoma Cells Against 5-Fluorouracil by Targeting Toll-Like Receptor 4
Rui-Peng Zheng,1 Dong-Kai Ma,2 Zhuo Li,3 Hai-Feng Zhang1 1Department of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of China; 2Department of Gastroenterology and Hepatology, Qian Wei Hospital of Jilin Province, Changch...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2020-07-01
|
| Series: | Cancer Management and Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/mir-145-regulates-the-chemoresistance-of-hepatic-carcinoma-cells-again-peer-reviewed-article-CMAR |
| _version_ | 1818118145870659584 |
|---|---|
| author | Zheng RP Ma DK Li Z Zhang HF |
| author_facet | Zheng RP Ma DK Li Z Zhang HF |
| author_sort | Zheng RP |
| collection | DOAJ |
| description | Rui-Peng Zheng,1 Dong-Kai Ma,2 Zhuo Li,3 Hai-Feng Zhang1 1Department of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of China; 2Department of Gastroenterology and Hepatology, Qian Wei Hospital of Jilin Province, Changchun, Jilin Province 130012, People’s Republic of China; 3Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of ChinaCorrespondence: Hai-Feng ZhangDepartment of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of ChinaTel +86 13756696677Email HaifengZhang159@outlook.comBackground: 5-fluorouracil (5-FU) is a common drug for hepatic carcinoma (HCC), but the drug resistance of clinical chemotherapy restricts its use. Studies have demonstrated that miRNA molecules can act as a chemoresistance regulator in drug resistance of tumors, whereas the role of miR-145 in the 5-FU-resistant HCC remains unclear.Objective: To explore the prognostic value of miR-145 in HCC and its molecular mechanism in 5-FU-resistant HCC cells.Methods: A qRT-PCR assay was conducted to quantify miR-145 in HCC tissues and 5-FU-resistant HCC cells. The Cell Counting Kit-8 (CCK-8) and flow cytometry were adopted to analyze the proliferation and apoptosis of 5-FU-resistant HCC cells. The Western blot was adopted to quantify toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and apoptosis-related proteins. Moreover, an in vivo tumor xenotransplantation of nude mice was conducted to determine the effect of miR-145 on 5-FU-resistant HCC cells.Results: MiR-145 was expressed lowly in HCC tissues and cells, and linked to high TNM staging and lymph node metastasis of HCC patients. Down-regulation of miR-145 indicated a poorer prognosis and it promoted drug resistance of HCC cells and inhibited cell apoptosis. In contrast, miR-145 overexpression improved the sensitivity of HCC cells to 5-FU and enhanced the inhibition of 5-FU on tumor growth. The luciferase reporter gene assay showed that TLR4 was the direct target of miR-145, and the Western blot assay revealed that overexpression of TLR4 reversed the inhibitory effect of miR-145 overexpression on TLR4 and MyD88 protein and the effects of it on apoptosis-related proteins.Conclusion: MiR-145 is an inhibiting factor in HCC and can target TLR4 to mediate the chemoresistance of HCC, which may provide novel ideas for treating HCC.Keywords: hepatic carcinoma, miR-145, toll-like receptor 4, TLR4, 5-fluorouracil, drug resistance |
| first_indexed | 2024-12-11T04:49:39Z |
| format | Article |
| id | doaj.art-10f5f13d56684dd488f431d3cf4250eb |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-11T04:49:39Z |
| publishDate | 2020-07-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-10f5f13d56684dd488f431d3cf4250eb2022-12-22T01:20:25ZengDove Medical PressCancer Management and Research1179-13222020-07-01Volume 126165617555553MiR-145 Regulates the Chemoresistance of Hepatic Carcinoma Cells Against 5-Fluorouracil by Targeting Toll-Like Receptor 4Zheng RPMa DKLi ZZhang HFRui-Peng Zheng,1 Dong-Kai Ma,2 Zhuo Li,3 Hai-Feng Zhang1 1Department of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of China; 2Department of Gastroenterology and Hepatology, Qian Wei Hospital of Jilin Province, Changchun, Jilin Province 130012, People’s Republic of China; 3Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of ChinaCorrespondence: Hai-Feng ZhangDepartment of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of ChinaTel +86 13756696677Email HaifengZhang159@outlook.comBackground: 5-fluorouracil (5-FU) is a common drug for hepatic carcinoma (HCC), but the drug resistance of clinical chemotherapy restricts its use. Studies have demonstrated that miRNA molecules can act as a chemoresistance regulator in drug resistance of tumors, whereas the role of miR-145 in the 5-FU-resistant HCC remains unclear.Objective: To explore the prognostic value of miR-145 in HCC and its molecular mechanism in 5-FU-resistant HCC cells.Methods: A qRT-PCR assay was conducted to quantify miR-145 in HCC tissues and 5-FU-resistant HCC cells. The Cell Counting Kit-8 (CCK-8) and flow cytometry were adopted to analyze the proliferation and apoptosis of 5-FU-resistant HCC cells. The Western blot was adopted to quantify toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and apoptosis-related proteins. Moreover, an in vivo tumor xenotransplantation of nude mice was conducted to determine the effect of miR-145 on 5-FU-resistant HCC cells.Results: MiR-145 was expressed lowly in HCC tissues and cells, and linked to high TNM staging and lymph node metastasis of HCC patients. Down-regulation of miR-145 indicated a poorer prognosis and it promoted drug resistance of HCC cells and inhibited cell apoptosis. In contrast, miR-145 overexpression improved the sensitivity of HCC cells to 5-FU and enhanced the inhibition of 5-FU on tumor growth. The luciferase reporter gene assay showed that TLR4 was the direct target of miR-145, and the Western blot assay revealed that overexpression of TLR4 reversed the inhibitory effect of miR-145 overexpression on TLR4 and MyD88 protein and the effects of it on apoptosis-related proteins.Conclusion: MiR-145 is an inhibiting factor in HCC and can target TLR4 to mediate the chemoresistance of HCC, which may provide novel ideas for treating HCC.Keywords: hepatic carcinoma, miR-145, toll-like receptor 4, TLR4, 5-fluorouracil, drug resistancehttps://www.dovepress.com/mir-145-regulates-the-chemoresistance-of-hepatic-carcinoma-cells-again-peer-reviewed-article-CMARhepatic carcinomamir-145toll-like receptor 4 (tlr4)5- fluorouracildrug resistance |
| spellingShingle | Zheng RP Ma DK Li Z Zhang HF MiR-145 Regulates the Chemoresistance of Hepatic Carcinoma Cells Against 5-Fluorouracil by Targeting Toll-Like Receptor 4 Cancer Management and Research hepatic carcinoma mir-145 toll-like receptor 4 (tlr4) 5- fluorouracil drug resistance |
| title | MiR-145 Regulates the Chemoresistance of Hepatic Carcinoma Cells Against 5-Fluorouracil by Targeting Toll-Like Receptor 4 |
| title_full | MiR-145 Regulates the Chemoresistance of Hepatic Carcinoma Cells Against 5-Fluorouracil by Targeting Toll-Like Receptor 4 |
| title_fullStr | MiR-145 Regulates the Chemoresistance of Hepatic Carcinoma Cells Against 5-Fluorouracil by Targeting Toll-Like Receptor 4 |
| title_full_unstemmed | MiR-145 Regulates the Chemoresistance of Hepatic Carcinoma Cells Against 5-Fluorouracil by Targeting Toll-Like Receptor 4 |
| title_short | MiR-145 Regulates the Chemoresistance of Hepatic Carcinoma Cells Against 5-Fluorouracil by Targeting Toll-Like Receptor 4 |
| title_sort | mir 145 regulates the chemoresistance of hepatic carcinoma cells against 5 fluorouracil by targeting toll like receptor 4 |
| topic | hepatic carcinoma mir-145 toll-like receptor 4 (tlr4) 5- fluorouracil drug resistance |
| url | https://www.dovepress.com/mir-145-regulates-the-chemoresistance-of-hepatic-carcinoma-cells-again-peer-reviewed-article-CMAR |
| work_keys_str_mv | AT zhengrp mir145regulatesthechemoresistanceofhepaticcarcinomacellsagainst5fluorouracilbytargetingtolllikereceptor4 AT madk mir145regulatesthechemoresistanceofhepaticcarcinomacellsagainst5fluorouracilbytargetingtolllikereceptor4 AT liz mir145regulatesthechemoresistanceofhepaticcarcinomacellsagainst5fluorouracilbytargetingtolllikereceptor4 AT zhanghf mir145regulatesthechemoresistanceofhepaticcarcinomacellsagainst5fluorouracilbytargetingtolllikereceptor4 |