si-TP73-AS1 suppressed proliferation and increased the chemotherapeutic response of GC cells to cisplatin

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Abstract

Previous studies have revealed that long noncoding RNAs (lncRNAs) function as crucial regulators in various biological processes, including tumorigenesis. Although the expression of lncRNA TP73-antisense RNA1 (AS1) has been identified in hepatocellular carcinoma and glioma, the biological function of TP73-AS1 in gastric cancer (GC) remains unclear. Thus, the present study employed a comprehensive analysis on the function of lncRNA TP73-AS1 in GC. The aim of the present study was to determine the clinical significance and biological function of TP73-AS1 in human GC tissues and cells. Additionally, the expression of TP73-AS1 was increased in GC tissues and cell lines and increased expression level of TP73-AS1 was associated with poor prognosis in patients with GC. Functional assays revealed that silencing of TP73-AS1 may suppress cell proliferation and enhance the chemotherapeutic response of GC cells to cisplatin through targeting the high mobility group 1/receptor for advanced glycation endproducts signaling pathway. Collectively, the results of the present study demonstrated that TP73-AS1 may be a novel lncRNA for the clinical prognosis of GC and a potential therapeutic target for the treatment of GC.

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Incidence and mortality of gastric cancer in China.

Ling Yang (2006)

Gastric cancer is one of the most frequent cancers in the world; almost two-thirds of gastric cancer cases and deaths occur in less developed regions. In China, based on two national mortality surveys conducted in 1970s and 1990s, there is an obvious clustering of geographical distribution of gastric cancer in the country, with the high mortality being mostly located in rural areas, especially in Gansu, Henan, Hebei, Shanxi and Shaanxi Provinces in the middle-western part of China. Despite a slight increase from the 1970s to early 1990s, remarkable declines in gastric cancer mortality were noticed in almost the entire population during the last decade in China. These declines were largely due to the dramatic improvements in the social-economic environment, lifestyle, nutrition, education and health care system after economic reforms started two decades ago. Nevertheless, gastric cancer will remain a significant cancer burden currently and be one of the key issues in cancer prevention and control strategy in China. It was predicted that, in 2005, 0.3 million deaths and 0.4 million new cases from gastric cancer would rank the third most common cancer. The essential package of the prevention and control strategy for gastric cancer in China would focus on controlling Helicobacter pylori (H. pylori) infection, improving educational levels, advocating healthy diet and anti-tobacco campaign, searching for cost-effective early detection, diagnosis and treatment programs including approaches for curable management and palliative care.

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Role of long non-coding RNA HULC in cell proliferation, apoptosis and tumor metastasis of gastric cancer: a clinical and in vitro investigation.

Yan Zhao, JIEJING CHEN, YUEMING SUN … (2013)

Long non-coding RNAs (lncRNAs) are emerging as key molecules in human cancer. Highly upregulated in liver cancer (HULC), an lncRNA, has recently been revealed to be involved in hepatocellular carcinoma development and progression. It remains unclear, however, whether HULC plays an oncogenic role in human gastric cancer (GC). In the present study, we demonstrated that HULC was significantly overexpressed in GC cell lines and GC tissues compared with normal controls, and this overexpression was correlated with lymph node metastasis, distant metastasis and advanced tumor node metastasis stages. In addition, a receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic values and the area under the ROC curve of HULC was up to 0.769. To uncover its functional importance, gain- and loss-of-function studies were performed to evaluate the effect of HULC on cell proliferation, apoptosis and invasion in vitro. Overexpression of HULC promoted proliferation and invasion and inhibited cell apoptosis in SGC7901 cells, while knockdown of HULC in SGC7901 cells showed the opposite effect. Mechanistically, we discovered that overexpression of HULC could induce patterns of autophagy in SGC7901 cells; more importantly, autophagy inhibition increased overexpression of HULC cell apoptosis. We also determined that silencing of HULC effectively reversed the epithelial-to-mesenchymal transition (EMT) phenotype. In summary, our results suggest that HULC may play an important role in the growth and tumorigenesis of human GC, which provides us with a new biomarker in GC and perhaps a potential target for GC prevention, diagnosis and therapeutic treatment.

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LncRNA SPRY4-IT1 sponges miR-101-3p to promote proliferation and metastasis of bladder cancer cells through up-regulating EZH2.

Miao Wang, Dong Teng Liu, Yawei Li … (2017)

Emerging evidences have indicated that long non-coding RNAs (LncRNAs) play vital roles in cancer development and progression. Previous studies have suggested that overexpression of SPRY4-IT1 predicates poor prognosis and promotes tumor progress in several cancers. However, the underlying mechanism of SPRY4-IT1 in bladder cancer remains unknown. In this study, we found that SPRY4-IT1 knockdown induced inhibition of cell proliferation, cell migration and invasion ability, and caused promotion of apoptosis in bladder cancer both in vitro and in vivo. Mechanistically, knockdown of SPRY4-IT1 increased the expression of miR-101-3p and subsequently inhibited the expression of EZH2 at posttranscriptional level. Importantly, SPRY4-IT1 could directly interact with miR-101-3p and down-regulation of miR-101-3p efficiently reversed the suppression of EZH2 induced by SPRY4-IT1 shRNA. Thus, SPRY4-IT1 positively regulated the expression of EZH2 through sponging miR-101-3p, and played an oncogenic role in bladder cancer progression. Together, our study elucidates the role of LncRNA SPRY4-IT1 as a miRNA sponge in bladder cancer, and sheds new light on LncRNA-directed diagnostics and therapeutics in bladder cancer.

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Author and article information

Journal

Journal ID (nlm-ta): Oncol Lett

Journal ID (iso-abbrev): Oncol Lett

Journal ID (publisher-id): OL

Title: Oncology Letters

Publisher: D.A. Spandidos

ISSN (Print): 1792-1074

ISSN (Electronic): 1792-1082

Publication date (Print): September 2018

Publication date (Electronic): 10 July 2018

Publication date PMC-release: 10 July 2018

Volume: 16

Issue: 3

Pages: 3706-3714

Affiliations

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China

Author notes

Correspondence to: Dr Jianjun Peng, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-Sen University, 2 Zhongshan Street, Guangzhou, Guangdong 510080, P.R. China, E-mail: jianjunpeng_q57@ 123456163.com

Article

Publisher ID: OL-0-0-9107

DOI: 10.3892/ol.2018.9107

PMC ID: 6096144

SO-VID: 2eabe9b9-3f8a-4151-9836-4099c9286f74

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.

si-TP73-AS1 suppressed proliferation and increased the chemotherapeutic response of GC cells to cisplatin

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Most cited references 30

Incidence and mortality of gastric cancer in China.

Role of long non-coding RNA HULC in cell proliferation, apoptosis and tumor metastasis of gastric cancer: a clinical and in vitro investigation.

LncRNA SPRY4-IT1 sponges miR-101-3p to promote proliferation and metastasis of bladder cancer cells through up-regulating EZH2.

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