MYH9 Promotes Growth and Metastasis via Activation of MAPK/AKT Signaling in Colorectal Cancer

Wang, Bin; Qi, Xiaolong; Liu, Jian; Zhou, Rui; Cao, Lin; Shangguan, Junjie; Zhang, Zhuoli; Zhao, Liang; Li, Guoxin

doi:10.7150/jca.27635

Cited by 66 publications

(65 citation statements)

References 35 publications

(43 reference statements)

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“…The functional annotation of OS- and RFS-related prediction miRNAs and their downstream genes showed the potential mechanisms of CRC. For example, the AMPK signaling pathway and Ras signaling pathway were associated with the OS of CRC reveled by KEGG analysis, and these results have been verified by other researchers [32,33].…”

Section: Discussionsupporting

confidence: 70%

Novel Multiple miRNA-Based Signatures for Predicting Overall Survival and Recurrence-Free Survival of Colorectal Cancer Patients

et al. 2019

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BackgroundColorectal cancer (CRC) has become a heavy health burden around the world, accounting for about 10% of newly diagnosed cancer cases. In the present study, we aimed to establish the miRNA-based prediction signature to assess the prognosis of CRC patients.Material/MethodsA total of 451 CRC patients’ expression profiles and clinical information were download from the TCGA database. LASSO Cox regression was conducted to construct the overall survival (OS)- and recurrence-free survival (RFS)-associated prediction signatures, by which CRC patients were divided into low- and high-risk groups. Kaplan-Meier (K-M) curve and receiver operating characteristic (ROC) curves were used to explore the discriminatory ability and stability of the signatures. Functional enrichment analyses were performed to identify the probable mechanisms.ResultsmiRNA-216a, miRNA-887, miRNA-376b, and miRNA-891a were used to build the prediction formula associated with OS, while miR-1343, miR-149, miR-181a-1, miR-217, miR-3130-1, miR-378a, miR-542, miR-6716, miR-7-3, miR-7702, miR-677, and miR-891a were obtained to construct the formula related to RFS. K-M curve and ROC curve revealed the good discrimination and efficiency of OS in the training (P<0.001, AUC=0.712) and validation cohorts (P=0.019, AUC=0.657), as well as the results of RFS in the training (P<0.001, AUC=0.714) and validation cohorts (P=0.042, AUC=0.651). The function annotations for the targeted genes of these miRNAs show the potential mechanisms of CRC.ConclusionsWe established 2 novel miRNA-based prediction signatures of OS and RFS, which are reliable tools to assess the prognosis of CRC patients.

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Section: Discussionsupporting

confidence: 70%

Novel Multiple miRNA-Based Signatures for Predicting Overall Survival and Recurrence-Free Survival of Colorectal Cancer Patients

et al. 2019

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“…MYH9 is recognized as an oncogene, as it is closely related to the progress and poor prognosis of most solid tumors 18‐20 . For example, MYH9 overexpression was induced by LIM kinase 1 (LIMK1) and promoted growth and metastasis by activating MAPK/AKT signaling in colorectal cancer 33,34 . The S100A4‐MYH9 axis could promote migration and invasion through inducing transforming growth factor‐β‐mediated epithelial‐mesenchymal transition in gastric cancer 35 .…”

Section: Discussionmentioning

confidence: 99%

FNDC3B 3′‐UTR shortening escapes from microRNA‐mediated gene repression and promotes nasopharyngeal carcinoma progression

Yang

et al. 2020

Cancer Science

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Alternative polyadenylation (APA), which induces shortening of the 3′‐UTR, is emerging as an important feature in cancer development and progression. Nevertheless, the effects and mechanisms of APA‐induced 3′‐UTR shortening in nasopharyngeal carcinoma (NPC) remain largely unclear. Fibronectin type III domain containing 3B (FNDC3B) tended to use proximal polyadenylation site and produce shorter 3′‐UTR according to our previous sequencing study. Herein, we found that FNDC3B with shorter 3′‐UTR could escape from miRNA‐mediated gene repression, and caused its increased expression in NPC. Knocking down of FNDC3B inhibited NPC cell proliferation, migration, invasion, and metastasis in vitro and in vivo. Overexpression of FNDC3B, especially those with shorter 3′‐UTR, promoted NPC progression. Furthermore, the mechanism study revealed that FNDC3B could bind to and stabilize myosin heavy chain 9 (MYH9) to activate the Wnt/β‐catenin signaling pathway. In addition, MYH9 could reverse the inhibitory effects of FNDC3B knockdown in NPC. Altogether, our results suggested that the 3′‐UTR shortening of FNDC3B mRNA mediated its overexpression in NPC and promoted NPC progression by targeting MYH9. This newly identified FNDC3B‐MYH9‐Wnt/β‐catenin axis could represent potential targets for individualized treatment in NPC.

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“…3 MYH9 is dysregulated and serves as an oncogene in many cancers; [4][5][6][7][8][9][10] however, its expression is positively associated with a good prognosis in patients with head and neck squamous cell carcinomas. 11 Moreover, researchers have reported that MYH9 promotes cell invasion and metastasis in gastric cancer, 12,13 facilitates cell growth and metastasis in colorectal cancer and pancreatic cancer, 14,15 and induces drug resistance in neuroblastoma. 16 However, the role of MYH9 in modulating HCC stemness has yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

Silencing MYH9 blocks HBx-induced GSK3β ubiquitination and degradation to inhibit tumor stemness in hepatocellular carcinoma

Lin

et al. 2020

Sig Transduct Target Ther

120

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MYH9 has dual functions in tumors. However, its role in inducing tumor stemness in hepatocellular carcinoma (HCC) is not yet determined. Here, we found that MYH9 is an effective promoter of tumor stemness that facilitates hepatocellular carcinoma pathogenesis. Importantly, targeting MYH9 remarkably improved the survival of hepatocellular carcinoma-bearing mice and promoted sorafenib sensitivity of hepatocellular carcinoma cells in vivo. Mechanistic analysis suggested that MYH9 interacted with GSK3β and reduced its protein expression by ubiquitin-mediated degradation, which therefore dysregulated the β-catenin destruction complex and induced the downstream tumor stemness phenotype, epithelial-mesenchymal transition, and c-Jun signaling in HCC. C-Jun transcriptionally stimulated MYH9 expression and formed an MYH9/GSK3β/β-catenin/c-Jun feedback loop. X protein is a hepatitis B virus (HBV)-encoded key oncogenic protein that promotes HCC pathogenesis. Interestingly, we observed that HBV X protein (HBX) interacted with MYH9 and induced its expression by modulating GSK3β/β-catenin/c-Jun signaling. Targeting MYH9 blocked HBX-induced GSK3β ubiquitination to activate the β-catenin destruction complex and suppressed cancer stemness and EMT. Based on TCGA database analysis, MYH9 was found to be elevated and conferred poor prognosis for hepatocellular carcinoma patients. In clinical samples, high MYH9 expression levels predicted poor prognosis of hepatocellular carcinoma patients. These findings identify the suppression of MYH9 as an alternative approach for the effective eradication of CSC properties to inhibit cancer migration, invasion, growth, and sorafenib resistance in HCC patients. Our study demonstrated that MYH9 is a crucial therapeutic target in HCC.

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MYH9 Promotes Growth and Metastasis via Activation of MAPK/AKT Signaling in Colorectal Cancer

Cited by 66 publications

References 35 publications

Novel Multiple miRNA-Based Signatures for Predicting Overall Survival and Recurrence-Free Survival of Colorectal Cancer Patients

Novel Multiple miRNA-Based Signatures for Predicting Overall Survival and Recurrence-Free Survival of Colorectal Cancer Patients

FNDC3B 3′‐UTR shortening escapes from microRNA‐mediated gene repression and promotes nasopharyngeal carcinoma progression

Silencing MYH9 blocks HBx-induced GSK3β ubiquitination and degradation to inhibit tumor stemness in hepatocellular carcinoma

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