<p>microRNA-548b suppresses aggressive phenotypes of hepatocellular carcinoma by directly targeting high-mobility group box 1 mRNA</p>
Authors: Peiqiang Jiang
Shiquan Li
Fanqi Meng
Zhennan Yun
Meng Yue
Journal: Cancer Management and Research (2019)
Discipline: CLINICAL MEDICINE
Keywords: HMGB1; PI3K–AKT pathway; hepatocellular carcinoma; high-mobility group box 1; microRNA-548b.
Affiliations: Department of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, People's Republic of China., Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, People's Republic of China.

Abstract:  Background and purpose: An increasing number of studies have revealed that microRNAs (miRNAs) are the main drivers of hepatocarcinogenesis including progression to later stages of liver cancer. Recently, miR-548b was identified as a cancer-related miRNA in glioma and tongue squamous cell carcinoma. Nonetheless, the expression pattern and specific roles of miR-548b in hepatocellular carcinoma (HCC) have not yet been clarified. Methods: Expression levels of miR-548b in HCC tissues and cell lines were measured by reverse-transcription quantitative PCR. In vitro and in vivo functional assays were performed to determine the effects of miR-548b on the malignant phenotypes of HCC cells. In addition, the molecular mechanisms by which miR-548b regulates the initiation and progression of HCC were investigated in detail. Results: miR-548b expression was weak in HCC tissues and cell lines. The low miR-548b expression significantly correlated with tumor size, TNM stage, and venous infiltration of HCC. In addition, exogenous miR-548b expression suppressed HCC cell proliferation, colony formation, and metastasis and induced apoptosis in vitro. Silencing of miR-548b exerted an opposite effect on these characteristics of HCC cells. Furthermore, miR-548b overexpression hindered tumor growth in vivo. Mechanistic analysis identified high-mobility group box 1 (HMGB1) as a direct target gene of miR-548b in HCC cells. Moreover, an HMGB1 knockdown reproduced the effects of miR-548b upregulation on HCC cells. Recovered HMGB1 expression reversed the effects of miR-548b on HCC cells. Notably, miR-548b overexpression deactivated the PI3K-AKT pathway in HCC cells in vitro and in vivo. Conclusion: Our findings provide the first evidence that miR-548b restrains HCC progression, at least partially, by downregulating HMGB1 and deactivating the PI3K-AKT pathway. Thus, miR-548b might be a novel target for the development of new therapies for HCC. 

Retracted: Yes

PubPeer comments:
 Figs 2D, 5D, 6D.  The apoptotic rates of Hep3B and SK-HEP-1 cells after transfection with miR-548b mimics or the miR-548b inhibitor were assessed by flow cytometry ;  Flow-cytometric analysis of the percentage of apoptotic cells ;  apoptosis... of the aforementioned cells were assessed by the ... flow cytometry . ![file] Bright green box marks a panel that also appeared in [Chen et al (2019)] . ![file] The horizontal axes are in slightly different locations, so the two versions are not identical. ![file] There may be matches with other panels, or with other papers in this oeuvre. https: docs.google.com spreadsheets d 1X401JM6CcpTSkbKsPsOl20pRKQ-ns1S_J5pTwtBjqPw edit?usp=sharing ---------------------------------------------------- UPDATE: Khaki box marks a panel that also appears in Figs 2D, 5D, 6D of [Liu et al (2019)] . ![] ![] , 
 *[left]* Fig 8A.  Photographs of tumor xenografts derived from Hep3B cells transfected with miR-548b mimics or negative control (NC) mimics . *[right]* Fig 8A from [Song et al (2019)] .  Images of tumor xenografts derived from miR-564 mimics or miR-NC-transfected TPC-1 cells . ![file] Different cell-lines, different treatments, different authors, same tumors (though rotated). , 
 Dear Hoya Camphorifolia Thank you very much for your comments. We are tracing the original data to further check your questions. We will correct it according to the problems. And also, we will let you know the result in time. , 
 #3 Another similarity! *[middle]* Fig 8A.  Photographs of tumor xenografts derived from Hep3B cells transfected with miR-548b mimics or negative control (NC) mimics . *[left]* Fig 8A from [Song et al (2019)] .  Images of tumor xenografts derived from miR-564 mimics or miR-NC-transfected TPC-1 cells . Rotated through 90 deg. *[right]* Fig 8A from [Kang et al (2019)] .  Representative images of tumor xenografts derived from nude mice implanted with agomiR-612 or agomiR-NCtransfected H522 cells . ![file] Coloured boxes indicate xenograft tumors that appear to be the same (slightly rotated). , 
 #4 ![file] *[left]* Fig 8A from [Song et al (2019)] . Now [retracted] . *[middle]* Fig 8A from [Yun et al (2019)] .  Photographs of tumor xenografts derived from Hep3B cells transfected with miR-548b mimics or negative control (NC) mimics . *[right]* Fig 8A from [Kang et al (2019)] . Now [retracted] . To be fair, Fig 8A from [Deng et al (2018)] involves the same band of ruler, but that paper has **not** been retracted. ![file] , 
 Retracted [4 October 2021] . ---------------------- The Editor and Publisher of Cancer Management and Research wish to retract the published article. Concerns were raised over alleged image duplication in Figures 6D and 8A with similar images from unrelated articles, specifically: - Figure 6D, panel Hep3B 1 appears to have been duplicated with a similar image in Figure 5D from Chen et al, 2019 . - Figure 6D, panel SK-HEP-1 6 appears to have been duplicated with a similar image in Figure 6D from Liu et al, 2019 . - Figure 8A, panels NC mimics 2 and miR-548b mimics 2 appear to have been duplicated with similar images in Figure 8A from Song et al, 2019 . The authors responded to our queries but were unable to provide a satisfactory explanation for the alleged duplication and could not provide satisfactory original data for their study. The Editor advised for the article to be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. ,