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靶向SNHG3/miR-186-5p通过调节食管癌中的METTL3逆转铂治疗引起的m6A水平升高。

Targeting SNHG3/miR-186-5p reverses the increased m6A level caused by platinum treatment through regulating METTL3 in esophageal cancer.

作者信息

Zhang Mingxin, Bai Minghua, Wang Li, Lu Ning, Wang Jia, Yan Rong, Cui Manli, Yan Honglin, Zhang Lingmin

机构信息

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Medical University, No. 48 Feng Hao West Road, Xi'an, 710077, Shaanxi, China.

Department of Health, Liaocheng People's Hospital, Liaocheng, 252000, Shandong, China.

出版信息

Cancer Cell Int. 2021 Feb 17;21(1):114. doi: 10.1186/s12935-021-01747-9.

Abstract

BACKGROUND

Platinum-based chemotherapy is a mainstay for treating esophageal cancer patients. In this manuscript, we have provided clues for influence of platinum on overall m6A level and further investigated the potential regulatory mechanism.

METHODS

qRT-PCR was used to measure SNHG3 and miR-186-5p expression; ELISA and western blot were used to measure the expression of METTL3. CCK8 was used to measure the cell proliferation rate. Caspase 3/7 activity was used to measure the apoptosis rate. Dual luciferase reporter gene assay and RNA pull down assay were used to investigate the potential crosstalk between miR-186-5p and SNHG3; and miR-186-5p and METTL3.

RESULTS

m6A level was increased when treated with platinum (CDDP, CPB and L-OHP). Besides, SNHG3 expression was induced and miR-186-5p expression was suppressed by platinum. Furthermore, SNHG3 could promote the m6A level, however miR-186-5p inhibited the m6A level through targeting METTL3. SNHG3 interacts with miR-186-5p to negatively regulate the expression of miR-186-5p; and miR-186-5p might bind to the 3'UTR of METTL3 to regulate its expression.

CONCLUSION

Platinum can increase the overall m6A level of esophageal cancer. SNHG3/miR-186-5p, induced by platinum, was involved in regulating m6A level by targeting METTL3. Our manuscript has provided clues that regulating m6A level might be a novel way to enhance the platinum efficacy.

摘要

背景

铂类化疗是治疗食管癌患者的主要手段。在本论文中,我们提供了铂对整体m6A水平影响的线索,并进一步研究了潜在的调控机制。

方法

采用qRT-PCR检测SNHG3和miR-186-5p的表达;采用ELISA和蛋白质免疫印迹法检测METTL3的表达。采用CCK8检测细胞增殖率。采用半胱天冬酶3/7活性检测细胞凋亡率。采用双荧光素酶报告基因检测法和RNA下拉实验研究miR-186-5p与SNHG3以及miR-186-5p与METTL3之间潜在的相互作用。

结果

用铂(顺铂、卡铂和奥沙利铂)处理后,m6A水平升高。此外,铂诱导SNHG3表达并抑制miR-186-5p表达。此外,SNHG3可促进m6A水平,而miR-186-5p通过靶向METTL3抑制m6A水平。SNHG3与miR-186-5p相互作用负向调节miR-186-5p的表达;miR-186-5p可能与METTL3的3'UTR结合以调节其表达。

结论

铂可提高食管癌的整体m6A水平。铂诱导的SNHG3/miR-186-5p通过靶向METTL3参与调控m6A水平。我们的论文提供了线索,表明调节m6A水平可能是增强铂疗效的新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0c3/7887820/c466cc3c4c71/12935_2021_1747_Fig1_HTML.jpg

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本文引用的文献

3
Recent advances in platinum-based chemotherapeutics that exhibit inhibitory and targeted mechanisms of action.
J Inorg Biochem. 2020 Jun;207:111070. doi: 10.1016/j.jinorgbio.2020.111070. Epub 2020 Mar 23.
4
Esophageal Cancer: An Updated Surveillance Epidemiology and End Results Database Analysis.
World J Oncol. 2020 Apr;11(2):55-64. doi: 10.14740/wjon1254. Epub 2020 Mar 29.
5
FTO promotes cell proliferation and migration in esophageal squamous cell carcinoma through up-regulation of MMP13.
Exp Cell Res. 2020 Apr 1;389(1):111894. doi: 10.1016/j.yexcr.2020.111894. Epub 2020 Feb 6.
6
7
The interplay between m6A RNA methylation and noncoding RNA in cancer.
J Hematol Oncol. 2019 Nov 22;12(1):121. doi: 10.1186/s13045-019-0805-7.

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