<p>MiR-145 Regulates the Chemoresistance of Hepatic Carcinoma Cells Against 5-Fluorouracil by Targeting Toll-Like Receptor 4</p>
Authors: Rui-Peng Zheng
Zhuo Li
Hai-Feng Zhang
Dong-Kai Ma
Journal: Cancer Management and Research (2020)
Discipline: CLINICAL MEDICINE
Keywords: 5-fluorouracil; TLR4; drug resistance; hepatic carcinoma; miR-145
Affiliations: Department of Interventional Therapy, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People's Republic of China., Department of Gastroenterology and Hepatology, Qian Wei Hospital of Jilin Province, Changchun, Jilin Province 130012, People's Republic of China., Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People's Republic of China.

Abstract:  Background: 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. 

Retracted: No

PubPeer comments:
 Fig 2C.  Apoptosis of designated cell strains treated through 5-FU according to the flow cytometry and apoptosis pattern . ![file] Fig 3E.  Apoptosis rate of Huh7 cells and Huh7 5-FU cells according to the flow cytometry. ![file] Each panel contains a halo of regularly-spaced dots, surrounding a central clump with a curious tapestry texture, almost woven in appearance (also visible in [Zhao et al 2020] ). Perhaps these are instrumentation artefacts of some kind. Is it possible for the authors to upload the raw data files to a data repository somewhere? , 
 There is a striking resemblance between the pointillated flow cytometry images and Western Blots in this paper and those in [RETRACTED] Lin Huang et al., The effect of LncRNA SNHG16 on vascular smooth muscle cells in CHD by targeting miRNA-218-5p, Experimental and Molecular Pathology 118 (2021) 104595, DOI: 10.1016 j.yexmp.2020.104595 - C4C2CAC6DC19711AB426B1F9968 ![file] , 
 Expression of Concern, [28 January 2022] . ------------------------------- The Editor and Publisher of *Cancer Management and Research* wish to issue an Expression of Concern for the published article. Following publication, concerns were raised about the scientific integrity of the articles content. We reached out to the authors requesting they supply information that would confirm the integrity of the data. However, the authors did not provide the requested files and could not satisfy our requirements to confirm the authenticity of some types of data. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. The authors have been notified about this Expression of Concern. ,