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Silence of long noncoding RNA UCA1 inhibits malignant proliferation and chemotherapy resistance to adriamycin in gastric cancer

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Abstract

Purpose

Urothelial carcinoma associated 1 (UCA1) gene is a long noncoding RNA (lncRNA), which shows expression and function abnormality in some kinds of malignant cancers. This study aimed to investigate its clinical significance and to examine its regulative effects of malignant proliferation and chemosensitivity to doxorubicin in gastric cancer cells.

Methods

The expression of UCA1 was detected by quantitative real-time PCR. Statistical analysis was used to determine the relationship between UCA1 expression and clinical features and the prognostic value of UCA1 for disease-free survival. MTT assay was used to detect cell proliferation ability and chemosensitivity. Dual-color flow cytometric method was used to detect cell apoptosis. The expression of cleaved PARP and Bcl-2 protein was examined by Western blot.

Results

UCA1 was highly expressed in gastric cancer tissues and cells, and its high expression level had a positive correlation with some malignant pathological characteristics of gastric cancer, such as higher grade and poor differentiation. Moreover, UCA1 was an independent prognostic biomarker of disease-free survival for gastric cancer patients. Silence of UCA1 could significantly inhibit the cell proliferation of gastric cancer BGC-823 and SGC7901 cells. The chemotherapy resistance to adriamycin of SGC7901/ADR cells was depressed by UCA1 silence, and IC50 for adriamycin presented a conspicuous depression. UCA1 silence advanced apoptosis induced by adriamycin in SGC7901/ADR cells, up-regulated cleaved PARP protein expression and depressed the expression of anti-apoptosis protein Bcl-2. These results demonstrated that chemotherapy resistance changes induced by UCA1 silence might be mediated by the cell apoptosis pathway.

Conclusions

In summary, lncRNA UCA1 was an independent prognostic biomarker of disease-free survival in gastric cancer patients and acted as an oncogene to regulate the malignant proliferation and resistance to adriamycin in gastric cancer cells. UCA1 might provide a new potential therapeutic target and stratagem for gastric cancer.

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Acknowledgments

This work was supported by the National Nature Science Foundation of China (81272716, 81172408) and Liaoning Social Development Research Plan (2012225016).

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Authors and Affiliations

  1. Department of Surgical Oncology, Affiliated First Hospital, China Medical University, Shenyang, 110004, China

    Chao Shang, Jiaxing Zhang & Baojun Huang

  2. Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, 110122, China

    Chao Shang

  3. Department of Central Laboratory, School of Stomatology, China Medical University, Shenyang, 110007, China

    Yan Guo

  4. No. 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning, China

    Baojun Huang

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  1. Chao Shang
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  2. Yan Guo
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  3. Jiaxing Zhang
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Correspondence to Baojun Huang.

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Shang, C., Guo, Y., Zhang, J. et al. Silence of long noncoding RNA UCA1 inhibits malignant proliferation and chemotherapy resistance to adriamycin in gastric cancer. Cancer Chemother Pharmacol 77, 1061–1067 (2016). https://doi.org/10.1007/s00280-016-3029-3

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  • DOI: https://doi.org/10.1007/s00280-016-3029-3

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