MSI2 knockdown represses extrahepatic cholangiocarcinoma growth and invasion by inhibiting epithelial&amp;ndash;mesenchymal transition

Hu, Feihu; Liu, Chenhai; Xie, Fang; Lin, Xiansheng; Yang, Ji Hyun; Wang, Chao; Huang, Qiang

doi:10.2147/ott.s170739

Cited by 6 publications

(9 citation statements)

References 35 publications

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“…Tumor size and metastasis are 2 key parameters for grading tumor stage. As expected, our meta-analysis of 6 studies enrolling 668 patients [ 8 , 11 , 13 , 15 , 16 , 22 ] suggested that increased MSI2 expression closely correlated advanced tumor stage (OR = 2.32, 95% CI: 1.60–3.38, P < .0001, fixed effects model, Fig. 2 D).…”

Section: Resultssupporting

confidence: 80%

“…Eight studies comprising 939 patients reported the link of MSI2 expression with tumor size. [8,9,11,13,15,16,21,22] The pooled result implied that higher MSI2 was marginally correlated with larger tumor size (OR = 1.58, 95% CI: 0.97–2.59, P = .07, random effects model, Fig. 2A).…”

Section: Resultsmentioning

confidence: 92%

“…Finally, 16 studies with 2203 patients with malignancy were included in our meta-analysis. [6][7][8][9][10][11][12][13][14][15][16][17][21][22][23][24] All the articles were cohort studies published between 2013 and 2021, which referred to leukemia, hepatocellular carcinoma (HCC), colorectal cancer (CRC), non-small cell lung cancer (NSCLC), oral squamous cell carcinoma (OSCC), bladder cancer (BC), gastric cancer (GC) and pancreatic cancer (PC). Eleven studies detected MSI2 expression by immunohistochemistry (IHC), while 5 studies examined MSI2 expression using polymerase chain reaction (PCR).…”

Section: Literature Selection and Study Characteristicsmentioning

confidence: 99%

“…[ 17 ] Also, the clinicopathological significance of MSI2 expression in malignancies is conflicting in terms of tumor size, tumor stage, differentiation, metastasis and so on. [ 9 , 11 , 12 , 15 ] The majority of studies exploring the prognostic value of MSI2 were limited by small sample size, which may account for those controversial results. Therefore, herein we conducted a meta-analysis of literatures to comprehensively analyze the clinicopathological and prognostic value of MSI2 expression in patients in pan-cancers.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic value of MSI2 expression in human malignancies: A PRISMA-compliant meta-analysis

Dong

et al. 2022

Medicine

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Background: The prognostic value of Musashi-2 (MSI2) in human malignancies remains controversial. We thus conducted this meta-analysis to evaluate the association between MSI2 expression and prognosis of patients with malignancies. Materials and Methods: We searched EMBASE, PubMed and Web of Science up to June 2021 for eligible studies. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated to assess the prognostic value of MSI2 expression. Odds ratios (ORs) with 95% CIs were calculated to evaluate the association between MSI2 expression and clinicopathological traits. Results: Sixteen studies involving 2203 patients were finally included in this meta-analysis. We found that high MSI2 expression might predict unfavorable OS (HR = 1.85, 95% CI: 1.62–2.10, P < .0001) and DFS/RFS (HR = 2.19, 95% CI: 1.87–2.57, P < .0001). Besides, the pooled results indicated that increased MSI2 expression correlated with large tumor size, poor tumor differentiation, positive lymph node metastasis and advanced tumor stage. Conclusions: Taken together, our data implies that MSI2 overexpression is related to poor survival outcomes in patients with malignancy. Therefore, MSI2 may serve as a novel prognostic biomarker and therapeutic target of malignancies. However, large-scale prospective and homogeneous investigations should be conducted in the future to further validate our findings.

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Section: Resultssupporting

confidence: 80%

Section: Resultsmentioning

confidence: 92%

Section: Literature Selection and Study Characteristicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prognostic value of MSI2 expression in human malignancies: A PRISMA-compliant meta-analysis

Dong

et al. 2022

Medicine

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“…We first found MSI2 silencing inhibited EGF-induced EMT in 2 PC cells, including inhibiting EGF-induced EMT-like cell morphology, EGF-enhanced cell invasion and migration, and EGF-stimulated change of EMT epithelia and mesenchyme markers. Similarly, MSI2 silencing represses extrahepatic cholangiocarcinoma growth and invasion by inhibiting EMT [33]. MSI2 silencing impairs cell proliferation and EMT in esophageal squamous cell carcinoma [34].…”

Section: Discussionmentioning

confidence: 97%

Musashi2 promotes EGF-induced EMT in pancreatic cancer via ZEB1-ERK/MAPK signaling

Sheng

Shi

Lin

et al. 2020

J Exp Clin Cancer Res

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Background: Our previous study showed Musashi2 (MSI2) promoted chemotherapy resistance and pernicious biology of pancreatic cancer (PC) by down-regulating Numb and p53. We further explored the novel molecular mechanism involving its oncogenic role in PC development. Methods: We investigated the potential role and mechanism of MSI2 in EGF-induced EMT in PC in vitro and vivo. Results: EGF enhanced EGFR (epidermal growth factor receptor) phosphorylation, induced EMT and activated ZEB1-ERK/MAPK signaling in 2 PC cells. However, MSI2 silencing reversed EGF stimulated function, including inhibiting EGF-promoted EMT-like cell morphology and EGF-enhanced cell invasion and migration. Meanwhile, MSI2 silencing inhibited EGF-enhanced EGFR phosphorylation at tyrosine 1068 and reversed EGF-induced change of the key proteins in EMT and ZEB1-ERK/MAPK signaling (ZEB1, E-cad, ZO-1, β-catenin, pERK and c-Myc). Additionally, MSI2 was co-stained and co-immunoprecipitated with ZEB1, pERK and c-Myc in PC cells by IF and co-IP, implying a close interaction between them. In vivo, MSI2 silencing inhibited pancreatic tumor size in situ and distant liver metastases. A close relationship of MSI2 with EMT and ZEB1-ERK/MAPK signaling were also observed in vivo and human PC samples, which coordinately promoted the poor prognosis of PC patients. Conclusions: MSI2 promotes EGF-induced EMT in PC via ZEB1-ERK/MAPK signaling.

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MSI2 regulates NLK-mediated EMT and PI3K/AKT/mTOR pathway to promote pancreatic cancer progression

Huang,

Sun,

et al. 2024

Cancer Cell Int

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Background The incidence of pancreatic cancer is increasing by years, and the 5-year survival rate is very low. Our team have revealed that Musashi2 (MSI2) could promote aggressive behaviors in pancreatic cancer by downregulating Numb and p53. MSI2 also facilitates EMT in pancreatic cancer induced by EGF through the ZEB1-ERK/MAPK signaling pathway. This study aims to further explore the molecular mechanisms of MSI2-regulated downstream pathways in pancreatic cancer. Methods In vitro and in vivo experiments were conducted to investigate the role and mechanism of MSI2 in promoting malignant behaviors of pancreatic cancer through regulation of NLK. Results Genes closely related to MSI2 were screened from the GEPIA and TCGA databases. We found that NLK showed the most significant changes in mRNA levels with consistent changes following MSI2 interference and overexpression. The high correlation between MSI2 and NLK was also observed at the protein level. Multivariate analysis revealed that both MSI2 and NLK were independent adverse indicators of survival in pancreatic cancer patients, as well as join together. In vitro, silencing or overexpressing NLK altered cell invasion and migration, by regulating EMT and the PI3K-AKT-mTOR pathway. Silencing MSI2 reduced protein expression in the EMT and PI3K-AKT-mTOR pathways, leading to decreased cell invasion and migration abilities, while these effects could be reversed by overexpression of NLK. In vivo, MSI2 silencing inhibited liver metastasis, which could be reversed by overexpressing NLK. Mechanistically, MSI2 directly binds to the translation regulatory region of NLK mRNA at positions 79–87 nt, enhancing its transcriptional activity and exerting post-transcriptional regulatory roles. The analysis of molecular docking showed the close relationship between MSI2 and NLK in pancreatic cancer patients. Conclusions Our findings elucidate the regulatory mechanisms of the MSI2-NLK axis in modulating aggressive behaviors of pancreatic cancer cells, which providing new evidence for therapeutic strategies in pancreatic cancer.

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MSI2 knockdown represses extrahepatic cholangiocarcinoma growth and invasion by inhibiting epithelial–mesenchymal transition

Cited by 6 publications

References 35 publications

Prognostic value of MSI2 expression in human malignancies: A PRISMA-compliant meta-analysis

Prognostic value of MSI2 expression in human malignancies: A PRISMA-compliant meta-analysis

Musashi2 promotes EGF-induced EMT in pancreatic cancer via ZEB1-ERK/MAPK signaling

MSI2 regulates NLK-mediated EMT and PI3K/AKT/mTOR pathway to promote pancreatic cancer progression

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