Effect of hnRNPA2B1-mediated m<sup>6</sup>A modification of MIR100HG in promoting the proliferation and invasion of gastric cancer MKN-28 cells

Lu Wenwen; Zhou Haixia; Zhuang Jianbo; Wang Jiemin; Zhang Jing

doi:10.13406/j.cnki.cyxb.003892

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Effect of hnRNPA2B1-mediated m⁶A modification of MIR100HG in promoting the proliferation and invasion of gastric cancer MKN-28 cells

Basic research | 更新时间：2025-10-22

- Effect of hnRNPA2B1-mediated m⁶A modification of MIR100HG in promoting the proliferation and invasion of gastric cancer MKN-28 cells
- Journal of Chongqing Medical University Vol. 50, Issue 8, Pages: 1078-1083(2025)
- 作者机构：
  
  1.苏州高新区人民医院消化内科，苏州 215129
  2.上海交通大学医学院附属第六人民医院消化内科，上海 200233
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003892
  CLC： R56
- Received：18 December 2023，
  
  Revised：2024-02-25，
  
  Accepted：28 March 2024，
  
  Published：28 August 2025
- 稿件说明：
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陆雯雯,周海霞,庄剑波,等.hnRNPA2B1介导m⁶A修饰MIR100HG促进胃癌MKN-28细胞增殖和侵袭作用[J].重庆医科大学学报,2025,50(8):1078-1083.

Lu Wenwen,Zhou Haixia,Zhuang Jianbo,et al.Effect of hnRNPA2B1-mediated m⁶A modification of MIR100HG in promoting the proliferation and invasion of gastric cancer MKN-28 cells[J].Journal of Chongqing Medical University,2025,50(8):1078-1083.
陆雯雯,周海霞,庄剑波,等.hnRNPA2B1介导m⁶A修饰MIR100HG促进胃癌MKN-28细胞增殖和侵袭作用[J].重庆医科大学学报,2025,50(8):1078-1083. DOI： 10.13406/j.cnki.cyxb.003892.

Lu Wenwen,Zhou Haixia,Zhuang Jianbo,et al.Effect of hnRNPA2B1-mediated m⁶A modification of MIR100HG in promoting the proliferation and invasion of gastric cancer MKN-28 cells[J].Journal of Chongqing Medical University,2025,50(8):1078-1083. DOI： 10.13406/j.cnki.cyxb.003892.

摘要

目的

探讨N

-甲基腺苷（N

-methyladenosine，m

A）阅读子异质核糖核蛋白A2/B1（heterogeneous nuclear ribonucleoprotein A2/B1，hnRNPA2B1）在人胃癌组织中的表达及其对人胃癌细胞系MKN-28（human gastric carinoma cell line MKN-28，MKN-28）增殖和侵袭的影响。

方法

利用癌症基因组图谱（the cancer genome atlas，TCGA）和基因表达数据集（gene expression omnibus，GEO）分析h

nRNPA2B1和长链非编码RNA（long non-coding RNA，lncRNA）miR-100-let-7a-2-miR-125b-1簇宿主基因（miR-100-let-7a-2-miR-125b-1 cluster host gene，MIR100HG）在胃癌组织的表达及其与患者临床生存预后的关系。实时荧光定量PCR（quantitative real-time PCR，qPCR）和蛋白质印迹法（Western blot）检测hnRNPA2B1对MIR100HG表达水平及其下游Wnt/β-连环蛋白信号通路（Wnt/β-catenin signaling pathway，Wnt/β-catenin）的影响；甲基化RNA免疫共沉淀（methylated RNA immunoprecipitation，MeRIP）检测MIR100HG的m

A水平；细胞计数试剂盒-8（cell counting kit-8，CCK-8）和Transwell小室实验检测细胞增殖和侵袭。

结果

与癌旁组织相比，hnRNPA2B1和MIR100HG在人胃癌组织的表达均升高（

=6.101，

0.001；

=2.191，

=0.037），且其高表达与胃癌患者预后不良显著相关。敲低hnRNPA2B1减少MIR100HG的mRNA表达水平（

=5.156，

=0.007）及其m

A水平（

=4.789，

=0.010）。敲低hnRNPA2B1抑制MKN-28细胞的增殖（

=4.915，

=0.008）和侵袭（

=5.167，

=0.007），并阻断Wnt/β-catenin信号通路的活性（均

0.05）；而过表达MIR100HG促进细胞增殖（

=3.578，

=0.023）和侵袭（

=8.411，

=0.001），激活Wnt/β-catenin信号通路（均

0.01），并逆转hnRNPA2B1敲低引起的抗肿瘤作用（

=3.667，

=0.021）。

结论

hnRNPA2B1介导m

A修饰MIR100HG和激活Wnt/β-catenin信号通路促进胃癌MKN-28细胞增殖和侵袭的作用。

Abstract

Objective

To investigate the expression of N

-methyladenosine（m

A） reader heterogeneous nuclear ribonucleoprotein A2/B1（hnRNPA2B1） in human gastric cancer（GC） tissue and its effect on the proliferation and invasion of MKN-28 cells.

Methods

The Cancer Genome Atlas and Gene Expression Omnibus were used to analyze the expression of hnRNPA2B1 and long noncoding RNA（lncRNA） mir-100-let-7a-2-mir-125b-1 cluster host gene（MIR100HG） in GC tissue and their association with the clinical prognosis of patients with GC. Quantitative PCR and Western blotting wer

e used to measure the effect of hnRNPA2B1 on the expression level of MIR100HG and its downstream Wnt/β-catenin signaling pathway； Methylated RNA immunoprecipitation（MeRIP） was used to measure the m

A level of MIR100HG；CCK-8 assay and Transwell assay were used to observe cell proliferation and invasion.

Results

Compared with paracancerous tissue，human GC tissue showed significant increases in the expression levels of hnRNPA2B1（

=6.101，

0.001） and MIR100HG（

=2.191，

=0.036 7），and the high expression levels of hnRNPA2B1 and MIR100HG were associated with poor survival in patients with GC. Knockdown of hnRNPA2B1 reduced the mRNA expression level（

=5.156，

=0.007） and m

A level of MIR100HG（

=4.789，

=0.010），inhibited the proliferation and invasion of MKN-28 cells（

=4.915，

=0.008 and

=5.167，

=0.007），and blocked the activity of the Wnt/β-catenin signaling pathway（

0.05）. Overexpression of MIR100HG promoted cell proliferation and invasion（

=3.578，

=0.023 and

=8.411，

=0.001），activated the Wnt/β-catenin signaling pathway（

0.01），and reversed the antitumor effect induced by hnRNPA2B1 knockdown（

=3.667，

=0.021）.

Conclusion

This study shows that hnRNPA2B1-mediated m6A modification of MIR100HG promotes the proliferation and invasion of GC MKN-28 cells by activating the Wnt/β-catenin signaling pathway.

关键词

Keywords

references

Siegel RL ， Miller KD ， Jemal A . Cancer statistics [J ] . CA A Cancer J Clinicians ， 2020 ， 70 （ 1 ）： 7 - 30 .

Chen XY ， Zhang J ， Zhu JS . The role of m 6 A RNA methylation in human cancer [J ] . Mol Cancer ， 2019 ， 18 （ 1 ）： 103 .

Wang Q ， Chen C ， Ding Q ， et al . METTL3-mediated m 6 A modification of HDGF mRNA promotes gastric cancer progression and has prognostic significance [J ] . Gut ， 2020 ， 69 （ 7 ）： 1193 - 1205 .

Fan HN ， Chen ZY ， Chen XY ， et al . METTL14-mediated m 6 A modification of circORC5 suppresses gastric cancer progressio n by regulating miR-30c-2-3p/AKT1S1 axis [J ] . Mol Cancer ， 2022 ， 21 （ 1 ）： 51 .

Zhou Y ， Wang Q ， Deng H ， et al . N6-methyladenosine demethylase FTO promotes growth and metastasis of gastric cancer via m 6 A modification of caveolin-1 and metabolic regulation of mitochondrial dynamics [J ] . Cell Death Dis ， 2022 ， 13 （ 1 ）： 72 .

Hu Y ， Gong C ， Li Z ， et al . Demethylase ALKBH5 suppresses invasion of gastric cancer via PKMYT1 m6A modification [J ] . Mol Cancer ， 2022 ， 21 （ 1 ）： 34 .

Chen XY ， Liang R ， Yi YC ， et al . The m 6 A reader YTHDF1 facilitates the tumorigenesis and metastasis of gastric cancer via USP14 translation in an m 6 A-dependent manner [J ] . Front Cell Dev Biol ， 2021 ， 9 ： 647702 .

Jiang F ， Tang X ， Tang C ， et al . HNRNPA2B1 promotes multiple myeloma progression by increasing AKT3 expression via m6A-dependent stabilization of ILF3 mRNA [J ] . J Hematol Oncol ， 2021 ， 14 （ 1 ）： 54 .

Rong L ， Xu Y ， Zhang K ， et al . HNRNPA2B1 inhibited SFRP2 and activated Wnt-β/catenin via m6A-mediated miR-106b-5p processing to aggravate stemness in lung adenocarcinoma [J ] . Pathol Res Pract ， 2022 ， 233 ： 153794 .

Zheng RJ ， Yu YH ， Lv LQ ， et al . m6A reader HNRNPA2B1 destabilization of ATG4B regulates autophagic activity，proliferation and olaparib sensitivity in breast cancer [J ] . Exp Cell Res ， 2023 ， 424 （ 1 ）： 113487 .

Wang S ， Ke H ， Zhang H ， et al . LncRNA MIR100HG promotes cell proliferation in triple-negative breast cancer through triplex formation with p27 loci [J ] . Cell Death Dis ， 2018 ， 9 （ 8 ）： 805 .

Chen FY ， Zhou ZY ， Zhang KJ ， et al . Long non-coding RNA MIR100HG promotes the migration，invasion and proliferation of triple-negative breast cancer cells by targeting the miR-5590-3p/OTX1 axis [J ] . Cancer Cell Int ， 2020 ， 20 ： 508 .

Liu H ， Li D ， Sun L ， et al . Interaction of lncRNA MIR100HG with hnRNPA2B1 facilitates m 6 A-dependent stabilization of TCF7L2 mRNA and colorectal cancer progression [J ] . Mol Cancer ， 2022 ， 21 （ 1 ）： 74 .

Peng WZ ， Zhao J ， Liu X ， et al . hnRNPA2B1 regulates the alternative splicing of BIRC5 to promote gastric cancer progression [J ] . Cancer Cell Int ， 2021 ， 21 （ 1 ）： 281 .

Li J ， Xu Q ， Wang W ， et al . MIR100HG：a credible prognostic biomarker and an oncogenic lncRNA in gastric cancer [J ] . Biosci Rep ， 2019 ， 39 （ 4 ）： BSR20190171 .

Wang Y ， Zheng L ， Shang W ， et al . Wnt/beta-catenin signaling confers ferroptosis resistance by targeting GPX4 in gastric cancer [J ] . Cell Death Differ ， 2022 ， 29 （ 11 ）： 2190 - 2202 .

Lu Y ， Zhao X ， Liu Q ， et al . lncRNA MIR100HG-derived miR-100 and miR-125b mediate cetuximab resistance via Wnt/β-catenin signaling [J ] . Nat Med ， 2017 ， 23 （ 11 ）： 1331 - 1341 .

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Related Institution

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⁰

Effect of hnRNPA2B1-mediated m6A modification of MIR100HG in promoting the proliferation and invasion of gastric cancer MKN-28 cells

DOI：10.13406/j.cnki.cyxb.003892

摘要

Abstract

关键词

Keywords

references

Effect of hnRNPA2B1-mediated m⁶A modification of MIR100HG in promoting the proliferation and invasion of gastric cancer MKN-28 cells