Upregulation of the long noncoding RNA UCA1 affects the proliferation, invasion, and survival of hypopharyngeal carcinoma

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Abstract

Background

Several long noncoding RNAs (lncRNAs) are involved in oncogenesis.

Methods and Results

Our microarray analysis showed that numerous lncRNAs are dysregulated in hypopharyngeal squamous cell carcinoma (HSCC) tumor tissues as compared with normal tissues. Among those lncRNAs, urothelial carcinoma-associated 1 (UCA1) has been found to have an oncogenic role in HSCC. We confirmed the upregulation of UCA1 in HSCC by assessing its expression levels in a cohort of 53 patient tumors and paired non-tumor samples. In addition, we found that high UCA1 expression was significantly associated with advanced T category, late clinical stage, greater lymphatic invasion, and worse prognosis. Furthermore, in vitro experiments demonstrated that UCA1 functioned as an oncogene by promoting the proliferation and invasion and preventing the apoptosis of HSCC cells.

Conclusions

Taken together, our findings for the first time identify the role of UCA1 as a tumor promoter and a pro-metastatic factor in HSCC, demonstrating that UCA1 is a potential prognostic biomarker and therapeutic target in HSCC.

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Most cited references 11

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Long non-coding RNA UCA1 increases chemoresistance of bladder cancer cells by regulating Wnt signaling.

Yu Fan, Bing Shen, Mingyue Tan … (2014)

Chemotherapy is a reasonable alternative to cystectomy in patients with invasive and advanced bladder cancer. However, bladder cancer cells often develop drug resistance to these therapies, and ~ 50% of patients with advanced bladder cancer do not respond to chemotherapy. Recent studies have shown that long non-coding RNA (lncRNA) is involved in the development of chemoresistance. Here we investigated the role of the urothelial cancer-associated 1 (UCA1) lncRNA in cisplatin resistance during chemotherapy for bladder cancer. We showed that cisplatin-based chemotherapy results in up-regulation of UCA1 expression in patients with bladder cancer. Similarly, UCA1 levels are increased in cisplatin-resistant bladder cancer cells. Over-expression of UCA1 significantly increases the cell viability during cisplatin treatment, whereas UCA1 knockdown reduces the cell viability during cisplatin treatment. UCA1 inhibition also partially overcomes drug resistance in cisplatin-resistant T24 cells. Furthermore, we showed that UCA1 positively regulates expression of wingless-type MMTV integration site family member 6 (Wnt6) in human bladder cancer cell lines. UCA1 and Wnt6 expression is also positively correlated in vivo. Up-regulation of UCA1 activates Wnt signaling in a Wnt6-dependent manner. We finally demonstrate that UCA1 increases the cisplatin resistance of bladder cancer cells by enhancing the expression of Wnt6, and thus represents a potential target to overcome chemoresistance in bladder cancer. © 2014 FEBS.

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National Cancer Database report on cancer of the head and neck: 10-year update.

K Mallin, R Weber, T Hoffman … (2009)

We sought to examine the current state of cancer care for head and neck tumors in the United States. We therefore performed a retrospective, longitudinal study of the approximately 822,000 head and neck cancer cases included in the National Cancer Data Base (NCDB) for 1990 through 2004, representing approximately 75% of the estimated incident diagnoses in the United States. All cases of head and neck cancer diagnosed and reported to the NCDB during this interval were reviewed, and descriptive statistics, grouped by disease and host factors, were analyzed over time and compared with a prior similar analysis done 10 years ago. Although many similarities persist, several major changes in head and neck cancer have occurred, most notably (1) a decrease in the number of the older-aged patients who have mucosally derived squamous cell carcinomas coupled with an increase in the number of younger-aged patients who have thyroid-origin adenocarcinomas and (2) a decrease in the use of radiation therapy alone for treatment in favor of chemotherapy enhanced radiation therapy. Head and neck cancers include a heterogeneous group of tumors whose precise composition changes over time and whose therapy evolves as well. The NCDB is well suited to capture this information and provide both an analysis of the current state of cancer care for head and neck tumors and a longitudinal view over time. (c) 2009 Wiley Periodicals, Inc.

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Is Open Access

Perspectives of Long Non-Coding RNAs in Cancer Diagnostics

Eduardo Reis, Sergio Verjovski-Almeida (2012)

Long non-coding RNAs (lncRNAs) transcribed from intergenic and intronic regions of the human genome constitute a broad class of cellular transcripts that are under intensive investigation. While only a handful of lncRNAs have been characterized, their involvement in fundamental cellular processes that control gene expression highlights a central role in cell homeostasis. Not surprisingly, aberrant expression of regulatory lncRNAs has been increasingly documented in different types of cancer, where they can mediate both oncogenic or tumor suppressor effects. Interaction with chromatin remodeling complexes that promote silencing of specific genes or modulation of splicing factor proteins seem to be two general modes of lncRNA regulation, but it is conceivable that additional mechanisms of action are yet to be unveiled. LncRNAs show greater tissue specificity compared to protein-coding mRNAs making them attractive in the search of novel diagnostics/prognostics cancer biomarkers in body fluid samples. In fact, lncRNA prostate cancer antigen 3 can be detected in urine samples and has been shown to improve diagnosis of prostate cancer. We suggest that an unbiased screening of the presence of RNAs in easily accessible body fluids such as serum and urine might reveal novel circulating lncRNAs as potential biomarkers in many types of cancer. Annotation and functional characterization of the lncRNA complement of the cancer transcriptome will conceivably provide new venues for early diagnosis and treatment of the disease.

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Author and article information

Contributors

Xinliang Pan: 531-82166781 , panxinl915@126.com

Dapeng Lei: 531-82166781 , leidapeng@sdu.edu.cn

Journal

Journal ID (nlm-ta): Mol Cancer

Journal ID (iso-abbrev): Mol. Cancer

Title: Molecular Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1476-4598

Publication date (Electronic): 21 March 2017

Publication date PMC-release: 21 March 2017

Publication date Collection: 2017

Volume: 16

Electronic Location Identifier: 68

Affiliations

[1 ]Department of Otorhinolaryngology, Qilu Hospital, Shandong University; Key Laboratory of Otolaryngology, NHFPC (Shandong University), 107 West Wenhua Road, Jinan, Shandong 250012 People’s Republic of China

[2 ]ISNI 0000 0004 1771 3402, GRID grid.412679.f, Department of Otolaryngology & Head and Neck Surgery, , 2nd Affiliated Hospital of Anhui Medical University, ; Hefei, China

[3 ]ISNI 0000 0001 2291 4776, GRID grid.240145.6, Department of Head and Neck Surgery, , The University of Texas MD Anderson Cancer Center, ; Houston, TX 77030 USA

[4 ]ISNI 0000 0001 2291 4776, GRID grid.240145.6, Department of Epidemiology, , The University of Texas MD Anderson Cancer Center, ; Houston, TX 77030 USA

Article

Publisher ID: 635

DOI: 10.1186/s12943-017-0635-6

PMC ID: 5361721

PubMed ID: 28327194

SO-VID: 9c75f3c0-30b5-4462-9177-558fd0e802b1

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 17 February 2017

Date accepted : 8 March 2017

Funding

Funded by: Taishan Scholars Program

Award ID: tshw20130950

Award Recipient : Guojun Li

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: long noncoding rnas,uca1,hypopharyngeal squamous cell carcinoma,prognosis

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: long noncoding rnas, uca1, hypopharyngeal squamous cell carcinoma, prognosis

Upregulation of the long noncoding RNA UCA1 affects the proliferation, invasion, and survival of hypopharyngeal carcinoma

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Abstract

Background

Methods and Results

Conclusions

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Karger: Oncology

Most cited references 11

Long non-coding RNA UCA1 increases chemoresistance of bladder cancer cells by regulating Wnt signaling.

National Cancer Database report on cancer of the head and neck: 10-year update.

Perspectives of Long Non-Coding RNAs in Cancer Diagnostics

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