The Journal of Practical Medicine >

2026 , Vol. 42 >Issue 4: 706 - 713

DOI: https://doi.org/10.3969/j.issn.1006-5725.2026.04.023

Reviews

Research progress on the regulatory mechanism of MYH9 in intestinal epithelial cells and related diseases

  • Yu XIA ,
  • Min DONG ,
  • Jinkui WU ,
  • Mengbin LI
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  • 1.Shaanxi University of Traditional Chinese Medicine，Xianyang 712000，Shaanxi，China
    2.Department of Gastroenterology，Xijing Hospital，Air Force Military Medical University，Xi'an 710000，Shaanxi，China
    3.Department of Oncology，Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine，Xianyang 712000，Shaanxi，China

Received date: 2025-09-17

  Online published: 2026-02-25

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Abstract

Myosin heavy chain 9（MYH9） serves as a fundamental regulator of the intestinal epithelial cytoskeletal architecture. Through its coordinated control of cytoskeletal dynamics and intercellular junction organization this molecular motor protein actively maintains epithelial barrier integrity while fine-tuning intestinal stem cell homeostasis?functions that demonstrate distinct dose-responsive characteristics. Under pathological stimuli，MYH9 manifests a context-dependent "double-edged sword" behavior. In inflammatory bowel disease， while complete MYH9 ablation compromises barrier function and amplifies inflammatory responses， its partial inhibition paradoxically enhances epithelial repair through activation of regenerative signaling cascades. During colorectal carcinogenesis， MYH9 fuels tumor progression by orchestrating MAPK/AKT signaling networks and synergizing with autophagy-related protein ATG9B to facilitate focal adhesion maturation. Furthermore， in pre-malignant conditions like intestinal metaplasia， MYH9 contributes to β-catenin pathway activation， thereby accelerating malignant transformation. This comprehensive review delineates the multifaceted regulatory networks governed by MYH9 in intestinal physiology and pathology， while proposing future investigative directions. Deciphering the context-specific functionality of MYH9 will not only advance targeted therapeutic development but also illuminate its promising utility as a liquid biopsy biomarker for gastrointestinal disorders.

Key words： myosin heavy chain 9; cytoskeleton; intestinal epithelial cells; inflammatory bowel disease; colorectal cancer

Cite this article

Yu XIA , Min DONG , Jinkui WU , Mengbin LI . Research progress on the regulatory mechanism of MYH9 in intestinal epithelial cells and related diseases[J]. The Journal of Practical Medicine, 2026 , 42(4) : 706 -713 . DOI: 10.3969/j.issn.1006-5725.2026.04.023

References

[1] LI Y， PAN Y， YANG X， et al. Unveiling the enigmatic role of MYH9 in tumor biology： a comprehensive review ［J］. Cell Commun Signal， 2024， 22（1）： 417. doi： 10.1186/s12964-024-01781-w .
[2] SIMONIN P， GUERRERO G L， BARDIN S， et al. The GTPase RAB6 is required for stem cell maintenance and cell migration in the gut epithelium ［J］. Development， 2024， 151（21）：dev203038. doi： 10.1242/dev.203038 .
[3] ZENG X F， WANG Y W， OU Y， et al. Role of myosin heavy chain 9 in gastrointestinal tumorigenesis： A comprehensive review ［J］. World J Gastrointest Oncol， 2025， 17（6）： 106617. doi： 10.4251/wjgo.v17.i6.106617 .
[4] PECCI A， MA X， SAVOIA A， et al. MYH9： Structure， functions and role of non-muscle myosin IIA in human disease ［J］. Gene， 2018， 664： 152-167. doi： 10.1016/j.gene.2018.04.048 .
[5] SABBIR M G， DILLON R， MOWAT M R. Dlc1 interaction with non-muscle myosin heavy chain II-A （Myh9） and Rac1 activation ［J］. Biol Open， 2016， 5（4）： 452-460. doi： 10.1242/bio.015859 .
[6] CAO M， WANG Y， XIAO Y， et al. Activation of the clock gene TIMELESS by H3k27 acetylation promotes colorectal cancer tumorigenesis by binding to Myosin-9 ［J］. J Exp Clin Cancer Res， 2021， 40（1）： 162. doi： 10.1186/s13046-021-01936-4 .
[7] YANG J S， CAO J M， SUN R， et al. SMYD4 promotes MYH9 ubiquitination through lysine monomethylation modification to inhibit breast cancer progression ［J］. Breast Cancer Res， 2025， 27（1）： 20. doi： 10.1186/s13058-025-01973-3 .
[8] HU S， REN S， CAI Y， et al. Glycoprotein PTGDS promotes tumorigenesis of diffuse large B-cell lymphoma by MYH9-mediated regulation of Wnt-β-catenin-STAT3 signaling ［J］. Cell Death Differ， 2022， 29（3）： 642-656. doi： 10.1038/s41418-021-00880-2 .
[9] LEE S， CHOI E， CHAE S， et al. Identification of MYH9 as a key regulator for synoviocyte migration and invasion through secretome profiling ［J］. Ann Rheum Dis， 2023， 82（8）： 1035-1048. doi： 10.1136/ard-2022-223625 .
[10] BONDZIE P A， CHEN H A， CAO M Z， et al. Non-muscle myosin-IIA is critical for podocyte f-actin organization， contractility， and attenuation of cell motility ［J］. Cytoskeleton， 2016， 73（8）： 377-395. doi： 10.1002/cm.21313 .
[11] CHEN Z， LIU C， ZHENG W， et al. MYH9 promotes malignant progression of glioma cells through regulating β-catenin stability via epithelial-mesenchymal transition signaling pathway ［J］. Sci Rep， 2025， 15（1）： 4618. doi： 10.1038/s41598-025-87151-z .
[12] YANG B， LIU H， BI Y， et al. MYH9 promotes cell metastasis via inducing Angiogenesis and Epithelial Mesenchymal Transition in Esophageal Squamous Cell Carcinoma ［J］. Int J Med Sci， 2020， 17（13）： 2013-2023. doi： 10.7150/ijms.46234 .
[13] YOU G R， CHANG J T， LI Y L， et al. MYH9 Facilitates Cell Invasion and Radioresistance in Head and Neck Cancer via Modulation of Cellular ROS Levels by Activating the MAPK-Nrf2-GCLC Pathway ［J］. Cells， 2022， 11（18）：2855. doi： 10.3390/cells11182855 .
[14] PERRIN L， MATIC VIGNJEVIC D. The emerging roles of the cytoskeleton in intestinal epithelium homeostasis ［J］. Semin Cell Dev Biol， 2023， 150-151： 23-27. doi： 10.1016/j.semcdb. 2023. 03.008 .
[15] KANG J S， LEE S J， LEE J H， et al. Angiotensin II-mediated MYH9 downregulation causes structural and functional podocyte injury in diabetic kidney disease ［J］. Sci Rep， 2019， 9（1）： 7679. doi： 10.1038/s41598-019-44194-3 .
[16] SUN H， ZHAO A， LI M， et al. Interaction of calcium binding protein S100A16 with myosin-9 promotes cytoskeleton reorganization in renal tubulointerstitial fibrosis ［J］. Cell Death Dis， 2020， 11（2）： 146. doi： 10.1038/s41419-020-2337-z .
[17] SUNG D C， AHMAD M， LERMA CERVANTES C B， et al. Mutations in non-muscle myosin 2A disrupt the actomyosin cytoskeleton in Sertoli cells and cause male infertility ［J］. Dev Biol， 2021， 470： 49-61. doi： 10.1016/j.ydbio.2020.11.003 .
[18] LIU Y， ZHANG T， ZHANG H， et al. Cell Softness Prevents Cytolytic T-cell Killing of Tumor-Repopulating Cells ［J］. Cancer Res， 2021， 81（2）： 476-488. doi： 10.1158/0008-5472.Can-20-2569 .
[19] 窦鑫，贺昌辉，梅笑，等. 基于“短链脂肪酸-肠屏障”途径探讨中药在腹泻型肠易激综合征中的干预研究进展 ［J］. 实用医学杂志， 2024， 40（15）： 2177-2182. doi： 10.3969/j.issn.1006-5725. 2024.15.023 .
[20] NAYDENOV N G， FEYGIN A， WANG D， et al. Nonmuscle Myosin IIA Regulates Intestinal Epithelial Barrier in vivo and Plays a Protective Role During Experimental Colitis ［J］. Sci Rep， 2016， 6： 24161. doi： 10.1038/srep24161 .
[21] NAAMA M， TELPAZ S， AWAD A， et al. Autophagy controls mucus secretion from intestinal goblet cells by alleviating ER stress ［J］. Cell Host Microbe， 2023， 31（3）： 433-446.e434. doi： 10.1016/j.chom.2023.01.006 .
[22] WANG S， LI S， LI Y， et al. Non-muscle myosin heavy chain 9 maintains intestinal homeostasis by preventing epithelium necroptosis and colitis adenoma formation ［J］. Stem Cell Reports， 2021， 16（5）： 1290-1301. doi： 10.1016/j.stemcr.2021.03.027 .
[23] REN X， LIU Q， ZHOU P， et al. DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells ［J］. Nat Commun， 2024， 15（1）： 3080. doi： 10.1038/s41467-024-47235-2
[24] WU H， MU C， XU L， et al. Host-microbiota interaction in intestinal stem cell homeostasis ［J］. Gut Microbes， 2024， 16（1）： 2353399. doi： 10.1080/19490976.2024.2353399 .
[25] ZHAO B， QI Z， LI Y， et al. The non-muscle-myosin-II heavy chain Myh9 mediates colitis-induced epithelium injury by restricting Lgr5+ stem cells ［J］. Nat Commun， 2015， 6： 7166. doi： 10.1038/ncomms8166 .
[26] WU J， XU X， DUAN J， et al. EFHD2 suppresses intestinal inflammation by blocking intestinal epithelial cell TNFR1 internalization and cell death ［J］. Nat Commun， 2024， 15（1）： 1282. doi： 10.1038/s41467-024-45539-x .
[27] AL-ALIEM A E E ABD， BADR E A E， EL-SHAYEB E I， et al. Association of the myosin heavy chain 9 gene single nucleotide polymorphism with inflammatory bowel disease ［J］. Biochem Biophys Rep， 2021， 28： 101113. doi： 10.1016/j.bbrep. 2021. 101113 .
[28] GE X， XUE G， DING Y， et al. The Loss of YTHDC1 in Gut Macrophages Exacerbates Inflammatory Bowel Disease ［J］. Adv Sci （Weinh）， 2023， 10（14）： e2205620. doi： 10.1002/advs. 202205620 .
[29] FENG L， WENG J， YAO C， et al. Extracellular Vesicles Derived from SIPA1（high） Breast Cancer Cells Enhance Macrophage Infiltration and Cancer Metastasis through Myosin-9 ［J］. Biology （Basel）， 2022， 11（4）：543. doi： 10.3390/biology11040543 .
[30] SINGH S K， SINHA S， PADHAN J， et al. MYH9 suppresses melanoma tumorigenesis， metastasis and regulates tumor microenvironment ［J］. Med Oncol， 2020， 37（10）： 88. doi： 10.1007/s12032-020-01413-6 .
[31] 王伟， 王敏， 成敏敏， 等. 红花多糖对结直肠癌小鼠肿瘤生长及磷脂酰肌醇3-激酶/蛋白激酶B/雷帕霉素靶蛋白信号通路的影响 ［J］. 实用医学杂志， 2025， 41（5）： 670-675. doi： 10.3969/j.issn.1006-5725.2025.05.008 .
[32] WANG B， QI X， LIU J， et al. MYH9 Promotes Growth and Metastasis via Activation of MAPK/AKT Signaling in Colorectal Cancer ［J］. J Cancer， 2019， 10（4）： 874-884. doi： 10.7150/jca. 27635 .
[33] WANG Z， ZHU Z， LI C， et al. NMIIA promotes tumorigenesis and prevents chemosensitivity in colorectal cancer by activating AMPK/mTOR pathway ［J］. Exp Cell Res， 2021， 398（1）： 112387. doi： 10.1016/j.yexcr.2020.112387 .
[34] LIU X， LIU Y， LIU Z， et al. CircMYH9 drives colorectal cancer growth by regulating serine metabolism and redox homeostasis in a p53-dependent manner ［J］. Mol Cancer， 2021， 20（1）： 114. doi： 10.1186/s12943-021-01412-9 .
[35] ZHONG Y， LONG T， GU C S， et al. MYH9-dependent polarization of ATG9B promotes colorectal cancer metastasis by accelerating focal adhesion assembly ［J］. Cell Death Differ， 2021， 28（12）： 3251-3269. doi： 10.1038/s41418-021-00813-z .
[36] SCHRAMEK D， SENDOEL A， SEGAL J P， et al. Direct in vivo RNAi screen unveils myosin IIa as a tumor suppressor of squamous cell carcinomas ［J］. Science， 2014， 343（6168）： 309-313. doi： 10.1126/science.1248627 .
[37] DERYCKE L， STOVE C， VERCOUTTER-EDOUART A S， et al. The role of non-muscle myosin IIA in aggregation and invasion of human MCF-7 breast cancer cells ［J］. Int J Dev Biol， 2011， 55（7-9）： 835-840. doi： 10.1387/ijdb.113336ld .
[38] XU Z， XIAO L， WANG S， et al. Alteration of gastric microbiota and transcriptome in a rat with gastric intestinal metaplasia induced by deoxycholic acid ［J］. Front Microbiol， 2023， 14： 1160821. doi： 10.3389/fmicb.2023.1160821 .
[39] WEI H， LI W， ZENG L， et al. OLFM4 promotes the progression of intestinal metaplasia through activation of the MYH9/GSK3β/β-catenin pathway ［J］. Mol Cancer， 2024， 23（1）： 124. doi： 10.1186/s12943-024-02016-9 .
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