Upregulation of miR-200b Inhibits Hepatocellular Carcinoma Cell Proliferation and Migration by Targeting HMGB3 Protein

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Abstract

HMGB3 belongs to the high-mobility group box subfamily and has been found to be overexpressed in gastric cancer. However, the expression and the role of HMGB3 in human hepatocellular carcinoma remain unknown. Here, we report that HMGB3, which is suppressed by miR-200b, contributes to cell proliferation and migration in human hepatocellular carcinoma. After analyzing The Cancer Genome Atlas data of 371 patients with hepatocellular carcinoma, we identified HMGB3 to be upregulated in human hepatocellular carcinoma tissue. Knockdown of HMGB3 in the hepatocellular carcinoma cell line suppressed cell proliferation and migration. TargetScan analysis showed miR-200b to be a possible regulator for HMGB3. Subsequent luciferase assays indicated that HMGB3 was a direct target of miR-200b. In addition, upregulation of miR-200b inhibited hepatocellular carcinoma cell growth and migration. HMGB3 overexpression or miR-200b downregulation was associated with poor prognosis. Our findings suggest HMGB3 may serve as an important oncoprotein whose expression is negatively regulated by miR-200b in hepatocellular carcinoma.

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Most cited references 28

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Global cancer statistics in the year 2000.

D Parkin (2001)

Estimation of the burden of cancer in terms of incidence, mortality, and prevalence is a first step to appreciating appropriate control measures in a global context. The latest results of such an exercise, based on the most recent available international data, show that there were 10 million new cases, 6 million deaths, and 22 million people living with cancer in 2000. The most common cancers in terms of new cases were lung (1.2 million), breast (1.05 million), colorectal (945,000), stomach (876,000), and liver (564,000). The profile varies greatly in different populations, and the evidence suggests that this variation is mainly a consequence of different lifestyle and environmental factors, which should be amenable to preventive interventions. World population growth and ageing imply a progressive increase in the cancer burden--15 million new cases and 10 million new deaths are expected in 2020, even if current rates remain unchanged.

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Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells.

James R. Downing, Hamish Spencer, T Somervaille … (2009)

The genetic programs that promote retention of self-renewing leukemia stem cells (LSCs) at the apex of cellular hierarchies in acute myeloid leukemia (AML) are not known. In a mouse model of human AML, LSCs exhibit variable frequencies that correlate with the initiating MLL oncogene and are maintained in a self-renewing state by a transcriptional subprogram more akin to that of embryonic stem cells (ESCs) than to that of adult stem cells. The transcription/chromatin regulatory factors Myb, Hmgb3, and Cbx5 are critical components of the program and suffice for Hoxa/Meis-independent immortalization of myeloid progenitors when coexpressed, establishing the cooperative and essential role of an ESC-like LSC maintenance program ancillary to the leukemia-initiating MLL/Hox/Meis program. Enriched expression of LSC maintenance and ESC-like program genes in normal myeloid progenitors and poor-prognosis human malignancies links the frequency of aberrantly self-renewing progenitor-like cancer stem cells (CSCs) to prognosis in human cancer.

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Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis.

G Zironi, M. Zanetti, L Gramantieri … (2001)

Hepatocellular carcinoma (HCC) is a major cause of death in cirrhotic patients. This neoplasm is associated with liver cirrhosis (LC) in more than 90% of cases. Early diagnosis and treatment of HCC are expected to improve survival of patients. To assess the cost effectiveness of a surveillance programme of patients with LC for the early diagnosis and treatment of HCC. A cohort of 313 Italian patients with LC were enrolled in the surveillance programme between March 1989 and November 1991. In the same period, 104 consecutive patients with incidentally detected HCC were referred to our centre and served as a control group. Surveillance was based on ultrasonography (US) and alpha fetoprotein (AFP) determinations repeated at six month intervals. Risk factors for HCC were assessed by multivariate analysis (Cox model). Outcome measures analysed were: (1) number and size of tumours; (2) eligibility for treatment; and (3) survival of patients. Economic issues were: (1) overall cost of surveillance programme; (2) cost per treatable HCC; and (3) cost per year of life saved (if any). Costs were assessed according to charges for procedures at our university hospital. Surveillance lasted a mean of 56 (31) months (range 6-100). During the follow up, 61 patients (19.5%) developed HCC (unifocal at US in 49 cases), with an incidence of 4.1% per year of follow up. AFP, Child-Pugh classes B and C, and male sex were detected as independent risk factors for developing HCC. Only 42 (68.9%) of 61 liver tumours were treated by surgical resection, orthotopic liver transplantation, or local therapy. The cumulative survival rate of the 61 patients with liver tumours detected in the surveillance programme was significantly longer than that of controls (p=0.02) and multivariate analysis showed an association between surveillance and survival. The overall cost of the surveillance programme was US$753 226, the cost per treatable HCC was US$17 934, and the cost for year of life saved was US$112 993. Our surveillance policy of patients with LC requires a large number of resources and offers little benefit in terms of patient survival. The decision whether to adopt a surveillance policy towards HCC should rely on the prevalence of the disease in the population and on the resources of a particular country.

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Author and article information

Journal

Journal ID (nlm-ta): Technol Cancer Res Treat

Journal ID (iso-abbrev): Technol. Cancer Res. Treat

Journal ID (publisher-id): TCT

Journal ID (hwp): sptct

Title: Technology in Cancer Research & Treatment

Publisher: SAGE Publications (Sage CA: Los Angeles, CA )

ISSN (Print): 1533-0346

ISSN (Electronic): 1533-0338

Publication date (Electronic): 21 October 2018

Publication date Collection: 2018

Volume: 17

Electronic Location Identifier: 1533033818806475

Affiliations

[1 ]Department of Cell Biology and Genetics, Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou, China

[2 ]Institute of Translational Medicine, Shenzhen Second People Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen, China

Author notes

[*]Dong-Yang Huang and Bin Liang, Department of Cell Biology and Genetics, Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Shantou University Medical College, Shantou 515041, China. Emails: huangdy@ 123456stu.edu.cn ; bliang@ 123456stu.edu.cn

Article

Publisher ID: 10.1177_1533033818806475

DOI: 10.1177/1533033818806475

PMC ID: 6198386

PubMed ID: 30343649

SO-VID: 61ca24a3-ac28-4acd-bc26-3076d2d96e45

License:

This article is distributed under the terms of the Creative Commons Attribution 4.0 License ( http://www.creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

History

Date received : 02 February 2018

Date revision received : 05 July 2018

Date accepted : 31 August 2018

Funding

Funded by: Guangdong Natural Science Foundation;

Award ID: 2104A030313473

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Keywords: hmgb3,mir-200b,human hepatocellular carcinoma,tumor progression,prognosis

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Keywords: hmgb3, mir-200b, human hepatocellular carcinoma, tumor progression, prognosis

Upregulation of miR-200b Inhibits Hepatocellular Carcinoma Cell Proliferation and Migration by Targeting HMGB3 Protein

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Microbiology Independent Research Journal (MIR Journal)

Most cited references 28

Global cancer statistics in the year 2000.

Hierarchical maintenance of MLL myeloid leukemia stem cells employs a transcriptional program shared with embryonic rather than adult stem cells.

Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis.

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