Musashi1 Promotes Non-Small Cell Lung Carcinoma Malignancy and Chemoresistance via Activating the Akt Signaling Pathway

Lang, Yaoguo; Kong, Xianglong; He, Chuanchao; Wang, Fengjiao; Liu, Benkun; Zhang, Shibo; Ning, Jinfeng; Zhu, Kaibin; Xu, Shidong

doi:10.1159/000485012

Cited by 26 publications

(31 citation statements)

References 32 publications

(39 reference statements)

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“…By ectopic expression of MSI1 in NSCLC cell lines, A549 and H522, phosphorylated Akt is increased and cancer cell proliferation is elevated. After inhibition of the Akt pathway through treating cell lines with MK2206 small molecules, proliferation of cancer cells decreases [30]. MSI1 is also required for tumorigenesis in medulloblastoma and reduction of its expression decreases neurosphere formation, cell proliferation, and tumor growth.…”

Section: Association Of Msi1 Expression and Cancersmentioning

confidence: 99%

Intracellular functions of RNA-binding protein, Musashi1, in stem and cancer cells

et al. 2020

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RNA-binding protein, musashi1 (MSI1), is a main protein in asymmetric cell division of the sensory organ precursor cells, whereas its expression is reported to be upregulated in cancers. This protein is a critical element in proliferation of stem and cancer stem cells, which acts through Wnt and Notch signaling pathways. Moreover, MSI1 modulates malignancy and chemoresistance of lung cancer cells via activating the Akt signaling. Due to the main role of MSI1 in metastasis and cancer development, MSI1 would be an appropriate candidate for cancer therapy. Downregulation of MSI1 inhibits proliferation of cancer stem cells and reduces the growth of solid tumors in several cancers. On the other hand, MSI1 expression is regulated by microRNAs in such a way that several different tumor suppressor miRNAs negatively regulate oncogenic MSI1 and inhibit migration and tumor metastasis. The aim of this review is summarizing the role of MSI1 in stem cell proliferation and cancer promotion.

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Section: Association Of Msi1 Expression and Cancersmentioning

confidence: 99%

Intracellular functions of RNA-binding protein, Musashi1, in stem and cancer cells

et al. 2020

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“…However, mice with kinase-inactive mutants are not [43]. Since the p-AKT/survivin pathway plays an important role in drug resistance in NSCLC, targeting EGFR itself, instead of its tyrosine kinase activity, could be a more efficient way to treat NSCLC, especially when the cancer cells are resistant to TKIs [44,45].…”

Section: Introductionmentioning

confidence: 99%

PLAUR Confers Resistance to Gefitinib Through EGFR/P-AKT/Survivin Signaling Pathway

Zhou

Kwak

Wu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Tyrosine kinase inhibitor gefitinib significantly improves the survival of patients with non-small-cell lung cancer (NSCLC) by inhibiting epidermal growth factor receptor (EGFR) tyrosine kinase. However, patients eventually develop resistance to gefitinib through uncharacterized mechanisms. It is known that plasminogen activator urokinase receptor (PLAUR) plays an important role in cell proliferation, migration and apoptosis. However, the role of PLAUR, particularly exosomal PLAUR in gefitinib resistance in NSCLC has not been reported. The aim of this study is to determine the relationship between PLAUR and gefitinib resistance. Methods: In this study, a tethered cationic lipoplex nanoparticle (TCLN) biochip containing molecular beacons was used as probes to detect PLAUR mRNA in plasma exosomes from patients with gefitinib-sensitive and -resistant NSCLC. In vitro, Real-time PCR was used to examine the expression of PLAUR mRNA and Western blot was applied to examine the expression of related proteins. The gene knockdown was achieved by Lentivirus based RNA silence technique. The cell counting kit-8 assay and EdU incorporation were used to examine cell proliferation. The flow cytometry was applied to determine cell apoptosis and cell cycle, while the mitochondrial membrane potential was measured by JC-1 dye assay. Signaling pathway affected by PLAUR knockdown was identified by cDNA Microarray. The effect of PLAUR knockdown on tumorigenesis was analyzed in vivo. Results: We found that the exosomal PLAUR mRNA in the plasma of gefitinib-resistant NSCLC patients was significantly increased compared to that of gefitinib-sensitive NSCLC patients. The PLAUR mRNA and soluble PLAUR protein were also significantly increased in gefitinib-resistant human lung adenocarcinoma PC9R cells compared to gefitinib-sensitive PC9 cells. Silencing PLAUR in PC9R cells impaired mitochondrial membrane potential and increased cell apoptosis via EGFR/p-AKT/survivin signaling pathway. Furthermore, EGFR was upregulated in the geftinib-resistant PC9R cells, and knockdown of EGFR significantly increased cell apoptosis. Conclusions: Taken together, our results demonstrated that PLAUR induces geftinib-resistance through EGFR/p-AKT/survivin signaling pathway in gefitinib-resistant human lung adenocarcinoma cells. PLAUR could be a novel therapeutic target for gefitinib-resistant NSCLC patients.

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“…NSCLC is typically carries a poor prognosis, with 5-year overall survival at around 15% [2]. Usually originating from peripheral lung tissues, lung adenocarcinoma (LAC) comprises more than 40% of lung cancers and has a high prevalence of distant metastasis [3]. The established curative method for managing LAC is surgical treatment.…”

Section: Introductionmentioning

confidence: 99%

MARCH9 Suppresses Lung Adenocarcinoma Progression by Downregulating ICAM-1

Shen

Wang

2018

Cell Physiol Biochem

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Background/Aims: To investigate the clinical significance and functional mechanisms of membrane-associated RING-CH protein 9 (MARCH9) in lung adenocarcinoma (LAC). Methods: Immunohistochemistry staining was performed to explore the expression of MARCH9 in LAC tissues and adjacent normal lung tissues. Patients’ prognosis was evaluated using overall survival. The prognostic role of MARCH9 was tested with univariate and multivariate analyses. To confirm the effect of MARCH9 in cell proliferation and invasion, overexpression of MARCH9 was induced in two LAC cell lines. Cell cycle, apoptosis, migration, invasion, and immunoprecipitation experiments were performed to further explore the signaling pathways involved. Results: Analysis of a series of 143 clinical samples revealed that MARCH9 was down-regulated in tumor tissues compared with normal lung tissues, and this was closely associated with lymph node metastasis (P = 0.004). Univariate and multivariate analyses indicated that MARCH9 was an independent prognostic biomarker for LAC; low MARCH9 expression indicated poor overall survival. Cellular studies with A549 and H1299 cells demonstrated that MARCH9 can attenuate tumor migration and invasion but had little effect on cell cycle or apoptosis. Moreover, an interaction between MARCH9 and ICAM-1 protein was identified, and overexpression of MARCH9 was found to attenuate the oncogenic effect of ICAM-1, suggesting that MARCH9 may inhibit tumor progression by downregulating ICAM-1 signaling. Conclusion: MARCH9 downregulation in LAC tissues correlated with poor clinical outcomes. MARCH9 may serve as a novel biomarker and potential therapeutic target for LAC.

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Musashi1 Promotes Non-Small Cell Lung Carcinoma Malignancy and Chemoresistance via Activating the Akt Signaling Pathway

Cited by 26 publications

References 32 publications

Intracellular functions of RNA-binding protein, Musashi1, in stem and cancer cells

Intracellular functions of RNA-binding protein, Musashi1, in stem and cancer cells

PLAUR Confers Resistance to Gefitinib Through EGFR/P-AKT/Survivin Signaling Pathway

MARCH9 Suppresses Lung Adenocarcinoma Progression by Downregulating ICAM-1

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