Mechanism of berberine inhibiting invasion and migration of renal carcinoma cells by down-regulating the expression of METTL3

YANG Tianyu; SHUAI Lixiong; XU Jingze; CHENG Xinyang; XU Zhiming; ZHANG Yongsheng

doi:10.6039/j.issn.1001-0408.2023.15.14

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Mechanism of berberine inhibiting invasion and migration of renal carcinoma cells by down-regulating the expression of METTL3

更新时间：2023-08-10

- Mechanism of berberine inhibiting invasion and migration of renal carcinoma cells by down-regulating the expression of METTL3
- ZHONGGUO YAOFANG Vol. 34, Issue 15, Pages: 1863-1868(2023)
- 作者机构：
  
  苏州大学附属第二医院病理科，江苏苏州　215004
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.15.14
  CLC： R965
- Published：15 August 2023，
  
  Received：30 January 2023，
  
  Revised：18 June 2023，
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杨天宇,帅立雄,许竞泽等.小檗碱通过下调METTL3表达抑制肾癌细胞侵袭和迁移的机制 ^Δ[J].中国药房,2023,34(15):1863-1868.

YANG Tianyu,SHUAI Lixiong,XU Jingze,et al.Mechanism of berberine inhibiting invasion and migration of renal carcinoma cells by down-regulating the expression of METTL3[J].ZHONGGUO YAOFANG,2023,34(15):1863-1868.
杨天宇,帅立雄,许竞泽等.小檗碱通过下调METTL3表达抑制肾癌细胞侵袭和迁移的机制 ^Δ[J].中国药房,2023,34(15):1863-1868. DOI： 10.6039/j.issn.1001-0408.2023.15.14.

YANG Tianyu,SHUAI Lixiong,XU Jingze,et al.Mechanism of berberine inhibiting invasion and migration of renal carcinoma cells by down-regulating the expression of METTL3[J].ZHONGGUO YAOFANG,2023,34(15):1863-1868. DOI： 10.6039/j.issn.1001-0408.2023.15.14.

摘要

目的

探讨小檗碱（BER）对人肾癌细胞侵袭、迁移的抑制作用及可能机制。

方法

以人肾癌OSRC-2细胞为对象进行实验。采用alamarBlue法测定0（对照组）、25、50、75、100、125、150、175、200 μmol/L BER作用24、48 h后对OSRC-2细胞增殖的抑制作用。用0（对照组）、50、100 μmol/L BER作用于细胞48 h后，通过流式细胞术分析BER对细胞周期的影响；通过细胞划痕实验观察24、36 h时各组细胞的迁移能力；通过Transwell实验观察作用24 h时各组细胞的侵袭能力；并通过Western blot法检测上述药物作用48 h后细胞中甲基转移酶样蛋白3（METTL3）的蛋白表达，通过RNA甲基化定量试剂盒检测各组细胞内RNA的N6-甲基腺嘌呤（m6A）水平。

结果

与对照组比较，不同浓度BER均可显著升高OSRC-2细胞的增殖抑制率（

＜0.01），并呈时间和浓度依赖性趋势；50、100 μmol/L BER作用48 h后可将细胞周期阻滞在G

期（

＜0.01）；50、100 μmol/L BER组细胞的迁移、侵袭能力均显著降低（

＜0.05或

＜0.01），细胞中METTL3蛋白的表达水平和RNA的m6A水平均显著降低（

＜0.01）。

结论

BER可通过下调METTL3的表达，进而抑制m6A水平，从而抑制人肾癌细胞的侵袭、迁移。

Abstract

OBJECTIVE

To investigate the inhibitory effect of berberine （BER） on the invasion and migration of human renal carcinoma cells and its potential mechanism.

METHODS

Using human renal carcinoma OSRC-2 cell as object， alamarBlue assay was adopted to detect the inhibitory effects of 0 （control group）， 25， 50， 75， 100， 125， 150， 175 and 200 μmol/L BER on the proliferation of OSRC-2 cell after treatment for 24 h and 48 h. After treated with 0（control group）， 50， 100 μmol/L BER for 48 h， the effect of BER on cell cycle was analyzed by flow cytometry. The migration of OSRC-2 cells in 24 h and 36 h was observed by cell scratch test， and the invasion ability of OSRC-2 cells in 24 h was detected by Transwell assay. The protein expression of methyltransferase-like 3 （METTL3） was detected by Western blot after treatment for 48 h， and RNA methylation quantification kit was used to detect the levels of N6-methyladenosine （m6A） in OSRC-2 cells.

RESULTS

Compared with control group， BER at different concentrations could significantly decrease the survival rate of OSRC-2 cells （

＜0.01）， and showed a dose-dependent and time-dependent manner. After 48 h of BER treatment at 50， 100 μmol/L， the cell was arrested in G

phase （

＜0.01）. Compared with control group， the migration and invasion abilities of cells in 50， 100 μmol/L BER group were significantly decreased （

＜0.05 or

＜0.01）； the protein expression of METTL3 and the level of m6A in RNA were significantly decreased（

＜0.01）.

CONCLUSIONS

BER can inhibit level of m6A by down-regulating the expression of METTL3， thereby inhibiting the invasion and metastasis of human renal carcinoma cells.

关键词

小檗碱人肾癌OSRC-2细胞迁移侵袭甲基转移酶样蛋白3N6-甲基腺嘌呤

Keywords

human renal carcinoma OSRC-2 cellmigrationinvasionmethyltransferase-like 3N6-methyladenosine

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