linc-ROR facilitates hepatocellular carcinoma resistance to doxorubicin by regulating TWIST1-mediated epithelial-mesenchymal transition

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Abstract

Long non-coding RNAs are associated with cancer progression. Long intergenic non-protein coding RNA (linc)-regulator of reprogramming (ROR) enhances tumor development in hepatocellular carcinoma (HCC). However, the effect of chemoresistance and its underlying mechanisms in HCC are not completely understood. The present study aimed to identify the effect of ROR on sensitivity to doxorubicin (DOX) in HCC cells. In the present study, Cell Counting Kit-8 and EdU assays were performed to assess cell viability and proliferation, respectively. In addition, E-cadherin and vimentin protein expression levels were assessed via western blotting and immunofluorescence. The results of the present study demonstrated that HCC cells with high linc-ROR expression levels were more resistant to DOX, and linc-ROR knockdown increased HCC cell DOX sensitivity compared with the control group. The results indicated that compared with the NC siRNA group, linc-ROR knockdown notably suppressed epithelial-mesenchymal transition by downregulating twist family bHLH transcription factor 1 (TWIST1) expression. TWIST1 knockdown displayed a similar effect on HCC cell DOX sensitivity to linc-ROR knockdown. Moreover, linc-ROR knockdown-induced HCC cell DOX sensitivity was inhibited by TWIST1 overexpression. The present study provided evidence that linc-ROR promoted HCC resistance to DOX by inducing EMT via interacting with TWIST1. Therefore, linc-ROR might serve as a therapeutic target for reducing DOX resistance in HCC.

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Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

Kenneth Livak, Thomas D. Schmittgen (2001)

The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-Delta Delta C(T)) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-Delta Delta C(T)) method. In addition, we present the derivation and applications of two variations of the 2(-Delta Delta C(T)) method that may be useful in the analysis of real-time, quantitative PCR data. Copyright 2001 Elsevier Science (USA).

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Cancer Statistics, 2017.

Rebecca Siegel, Kimberly D Miller, Ahmedin Jemal (2017)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics. In 2017, 1,688,780 new cancer cases and 600,920 cancer deaths are projected to occur in the United States. For all sites combined, the cancer incidence rate is 20% higher in men than in women, while the cancer death rate is 40% higher. However, sex disparities vary by cancer type. For example, thyroid cancer incidence rates are 3-fold higher in women than in men (21 vs 7 per 100,000 population), despite equivalent death rates (0.5 per 100,000 population), largely reflecting sex differences in the "epidemic of diagnosis." Over the past decade of available data, the overall cancer incidence rate (2004-2013) was stable in women and declined by approximately 2% annually in men, while the cancer death rate (2005-2014) declined by about 1.5% annually in both men and women. From 1991 to 2014, the overall cancer death rate dropped 25%, translating to approximately 2,143,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the cancer death rate was 15% higher in blacks than in whites in 2014, increasing access to care as a result of the Patient Protection and Affordable Care Act may expedite the narrowing racial gap; from 2010 to 2015, the proportion of blacks who were uninsured halved, from 21% to 11%, as it did for Hispanics (31% to 16%). Gains in coverage for traditionally underserved Americans will facilitate the broader application of existing cancer control knowledge across every segment of the population. CA Cancer J Clin 2017;67:7-30. © 2017 American Cancer Society.

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Epithelial-mesenchymal transitions: twist in development and metastasis.

Yibin Kang, Joan Massagué (2004)

Epithelial-mesenchymal transitions (EMT) are vital for morphogenesis during embryonic development and are also implicated in the conversion of early stage tumors into invasive malignancies. Several key inducers of EMT are transcription factors that repress E-cadherin expression. A recent report in Cell (Yang et al., 2004) adds Twist to this list and links EMT to the ability of breast cancer cells to enter the circulation and seed metastases.

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Author and article information

Journal

Journal ID (nlm-ta): Mol Med Rep

Journal ID (iso-abbrev): Mol Med Rep

Title: Molecular Medicine Reports

Publisher: D.A. Spandidos

ISSN (Print): 1791-2997

ISSN (Electronic): 1791-3004

Publication date (Print): May 2021

Publication date (Electronic): 09 March 2021

Publication date PMC-release: 09 March 2021

Volume: 23

Issue: 5

Electronic Location Identifier: 340

Affiliations

[1 ]Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China

[2 ]Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China

[3 ]Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China

[4 ]Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China

[5 ]Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China

Author notes

Correspondence to: Dr Weilin Wang or Dr Dongkai Zhou, Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, Zhejiang 310009, P.R. China, E-mail: wam@ 123456zju.edu.cn , E-mail: dkzhou@ 123456zju.edu.cn

[*]

Contributed equally

Article

Publisher ID: MMR-0-0-11979

DOI: 10.3892/mmr.2021.11979

PMC ID: 7974311

PubMed ID: 33760121

SO-VID: a4cf6621-8802-4691-8c27-0f44689b50be

License:

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

History

Date received : 17 July 2020

Date accepted : 22 December 2020

Funding

Funded by: Science and Technology Department Public Welfare Project of Zhejiang Province

Award ID: LGF18H160023

Funded by: Administration of Traditional Chinese Medicine of Zhejiang Province

Award ID: 2015ZA012

Funded by: National Natural Science Foundation of China, open-funder-registry 10.13039/501100001809;

Award ID: 81572307

Award ID: 81773096

Award ID: 81701630

Funded by: Major Project of Medical and Health Technology Development Program in Zhejiang Province

Award ID: 7211902

Funded by: Zhejiang Provincial Medical and Health Research Project

Award ID: 2018KY126

Award ID: 2021KY030

Funded by: Projects of Lishui Key Research and Development Plan in Zhejiang Province

Award ID: 2017ZDYF12

The present study was supported by the Science and Technology Department Public Welfare Project of Zhejiang Province (grant no. LGF18H160023), the Administration of Traditional Chinese Medicine of Zhejiang Province (grant no. 2015ZA012), The National Natural Science Foundation of China (grant nos. 81572307, 81773096 and 81701630), the Major Project of Medical and Health Technology Development Program in Zhejiang Province (grant no. 7211902), the Zhejiang Provincial Medical and Health Research Project (grant nos. 2018KY126 and 2021KY030) and the Projects of Lishui Key Research and Development Plan in Zhejiang Province (grant no. 2017ZDYF12).

linc-ROR facilitates hepatocellular carcinoma resistance to doxorubicin by regulating TWIST1-mediated epithelial-mesenchymal transition

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Karger: Oncology

Most cited references 47

Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

Cancer Statistics, 2017.

Epithelial-mesenchymal transitions: twist in development and metastasis.

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