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Published on: April 25, 2018
Long non-coding RNA XIST negatively regulates thoracic aortic aneurysm cell proliferation by targeting the
Ming Zhu1, Mengwei Tan2, Fazhen Xu1
1Department of Cardiovascular Surgery, Huizhou Municipal Central Hospital, Huizhou, 516001, China. zhuming2022@yandex.com.
Abstract:
Non-coding RNAs (ncRNAs) are important molecular modulators in diverse pathological processes, influencing the occurrence and progression of carcinomas. Thoracic aortic aneurysm (TAA) is an infrequent disease among aneurysmal diseases and accounts for nearly 3% of diagnosed aneurysms. The functional roles of long ncRNA (lncRNA) XIST and miR-193a-5p and the associated molecular mechanisms are yet to be investigated. In the current study, we discovered that miR-193a-5p was expressed at low levels in the blood of TAA patients. Further, loss-of-function and gain-of-function assays disclosed that miR-195-3p impacted the proliferation ability of TAA cells. XIST was found to be the most overexpressed lncRNA among predicted lncRNAs binding to miR-193a-5p. The promotive function of XIST in TAA was also explored. Subsequently, KLF7 was proved to be the downstream factor of the XIST/miR-193a-5p axis. Rescue assays testified the whole regulation mechanism of the XIST/miR-193a-5p/KLF7 axis in TAA. MiR-193a-5p was absorbed by XIST for the improvement of KLF7 in TAA. These results concluded that XIST might be engaged in TAA pathogenesis via regulation of the miR-193a-5p/KLF7 axis, supplementing more therapeutic options for TAA treatment.
Insights
Long non-coding RNA XIST promotes thoracic aortic aneurysm (TAA) by sponging miR-193a-5p, leading to increased KLF7 expression. This molecular pathway offers potential therapeutic targets for TAA treatment.
Area of Science:
- Molecular Biology
- Genetics
- Cardiovascular Research
Background:
- Non-coding RNAs (ncRNAs) are key regulators in disease pathogenesis.
- Thoracic aortic aneurysm (TAA) is a rare but serious vascular condition.
- The specific roles of lncRNA XIST and miR-193a-5p in TAA remain unclear.
Purpose of the Study:
- To investigate the functional roles of lncRNA XIST and miR-193a-5p in TAA.
- To elucidate the molecular mechanisms underlying XIST and miR-193a-5p involvement in TAA.
- To identify potential therapeutic targets for TAA.
Main Methods:
- Analysis of miR-193a-5p expression in TAA patient blood samples.
- In vitro loss-of-function and gain-of-function assays on TAA cells.
- Identification and validation of lncRNA XIST as a target of miR-193a-5p.
- Investigation of KLF7 as a downstream effector in the XIST/miR-193a-5p pathway.
- Rescue experiments to confirm the regulatory axis.
Main Results:
- miR-193a-5p expression was significantly decreased in TAA patients.
- miR-193a-5p levels influenced TAA cell proliferation.
- XIST was identified as a highly overexpressed lncRNA sponging miR-193a-5p.
- The XIST/miR-193a-5p/KLF7 axis was confirmed to regulate TAA progression.
- XIST promotes TAA by upregulating KLF7 via miR-193a-5p inhibition.
Conclusions:
- XIST plays a crucial role in TAA pathogenesis.
- The XIST/miR-193a-5p/KLF7 axis represents a novel regulatory mechanism in TAA.
- Targeting this axis may offer new therapeutic strategies for TAA.
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