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Long non-coding RNA X-inactive-specific transcript contributes to cisplatin resistance in gastric cancer by sponging
Xiao Han1, Hai-Bin Zhang, Xue-Di Li
1Internal Medicine-Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
Abstract:
X-inactive-specific transcript (XIST) is a 19 kb noncoding RNA which is oncogenic in many cancers including gastric cancer. It is reported that XIST contributes to gastric cancer cells resistant to cisplatin, but specific mechanisms governing this resistance remain unclear. We firstly examined the XIST level in gastric cancer cells and tumor specimens. We confirmed that XIST is overexpressed in gastric cancer cells and tumors, which further contributed to the poor prognosis of patients with gastric cancer. We also confirmed that high XIST level contributes to the cisplatin resistance in gastric cancer cells. Subsequently, we predicted microRNAs that have the potential to interact with XIST and found that Let-7b-5p may directly interact with XIST. We confirmed the direct interaction between XIST and Let-7b-5p and identified a negative correlation between the level of Let-7b-5p and XIST in gastric cancer tumors. Meanwhile, Let-7b-5p inhibitor treatment can partially rescued the effect of XIST-specific small interfering RNA on cell proliferation and apoptosis by regulating Aurora kinase B expression. XIST functions as an oncogene in gastric cancer which contributes to the cisplatin resistance by interacting with Let-7b-5p.
Insights
X-inactive-specific transcript (XIST) is overexpressed in gastric cancer, promoting cisplatin resistance. This oncogenic noncoding RNA interacts with Let-7b-5p, impacting cancer cell survival and treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- X-inactive-specific transcript (XIST) is a 19 kb noncoding RNA with oncogenic roles in various cancers, including gastric cancer.
- XIST is implicated in cisplatin resistance in gastric cancer cells, but the underlying mechanisms are not fully understood.
Purpose of the Study:
- To investigate the role of XIST in gastric cancer and its contribution to cisplatin resistance.
- To identify potential molecular interactions involving XIST in gastric cancer.
Main Methods:
- Quantification of XIST levels in gastric cancer cells and patient tumor specimens.
- Bioinformatic prediction and experimental validation of microRNA interactions with XIST.
- Assessment of the impact of XIST and microRNA modulation on gastric cancer cell behavior and gene expression.
Main Results:
- XIST is overexpressed in gastric cancer cells and tumors, correlating with poor patient prognosis.
- High XIST levels are associated with increased cisplatin resistance in gastric cancer cells.
- Let-7b-5p was identified as a direct interaction partner of XIST, with an inverse correlation in tumor tissues.
- Modulation of Let-7b-5p partially rescued the effects of XIST knockdown on cell proliferation and apoptosis via Aurora kinase B regulation.
Conclusions:
- XIST acts as an oncogene in gastric cancer, conferring cisplatin resistance through its interaction with Let-7b-5p.
- The XIST/Let-7b-5p axis represents a potential therapeutic target for overcoming cisplatin resistance in gastric cancer.
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