CD73/NT5E is a target of miR-30a-5p and plays an important role in the pathogenesis of non-small cell lung cancer

Zhu, Jianjie; Zeng, Yuanyuan; Li, Wei; Qin, Hualong; Li, Zhe; Shen, Dan; Gu, Danan; Huang, Jianan; Liu, Zeyi

doi:10.1186/s12943-017-0591-1

Cited by 131 publications

(142 citation statements)

References 44 publications

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“…Furthermore, in patients with EGFR mutation‐negative NSCLC, expression of CD73 was not associated with the outcome of treatment with ICIs, unlike the situation in patients who were EGFR mutation‐positive. Our findings appear to be consistent with those of previous preclinical studies, which have shown that the mechanism of CD73‐induced immune tolerance involves the EGFR signaling pathway …”

Section: Discussionsupporting

confidence: 92%

Predictive value of CD73 expression for the efficacy of immune checkpoint inhibitors in NSCLC

et al. 2020

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Background CD73 induces the dephosphorylation of adenosine monophosphate converting it to adenosine, enabling malignancies to escape from immune surveillance. Although CD73 overexpression has been reported to be a poor prognostic factor in several malignancies including non‐small cell lung cancer (NSCLC), its predictive relevance in NSCLC patients receiving immune checkpoint inhibitors is unknown. The present research was conducted to investigate the prognostic significance of CD73 expression in NSCLC patients receiving immune checkpoint inhibitors (ICIs). Methods We screened 91 patients with advanced or recurrent NSCLC who received immune checkpoint inhibitors. CD73 expression was evaluated immunohistochemically using tissue specimens obtained just before treatment with ICIs. Results Analysis of progression‐free survival (PFS) and overall survival (OS) in relation to several levels of CD73 expression (1%, 10%, 30%, and 50%) showed that both tended to be more favorable as expression of CD73 increased. PFS and OS were longer for patients in whom at least 50% of the tumor cells expressed CD73 than for those in whom <50% of the tumor cells did so. In patients who were positive for EGFR mutation, immune checkpoint inhibitors were significantly more effective in those with high CD73 expression, whereas CD73 expression did not significantly affect the efficacy in patients with EGFR mutation‐negative NSCLC. Furthermore, CD73 expression was predictive factor for the PFS independent of PD‐L1 expression in patients with EGFR mutation. Conclusions High CD73 expression may predict a favorable response to ICIs in NSCLC patients, especially those harboring EGFR mutations. Key points Significant findings of the study: In patients who were positive for EGFR mutation, immune checkpoint inhibitors (ICIs) were significantly more effective in those with high CD73 expression, whereas CD73 expression did not significantly affect the efficacy in patients with EGFR mutation‐negative NSCLC. What this study adds: High CD73 expression may predict a favorable response to immune checkpoint inhibitors in NSCLC patients, especially those harboring EGFR mutations.

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Section: Discussionsupporting

confidence: 92%

Predictive value of CD73 expression for the efficacy of immune checkpoint inhibitors in NSCLC

et al. 2020

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“…MiRNA array data from our previous study showed that 15 miRNA expressions were significantly upregulated in lung carcinoma compared to normal lung tissues A).…”

Section: Resultsmentioning

confidence: 96%

“…MiRNA array data from our previous study showed that 15 miRNA expressions were significantly upregulated in lung carcinoma compared to normal lung tissues. 6,21 More specifically, seven miRNAs (miR-183-5p, miR-193b-3p, miR-210, miR-21-5p, miR-224-5p, miR-4286, and miR-96-5p, log2 fold change ≥2.0, P < 0.05) were upregulated ( Figure 1A). Among these, miR-210 and miR-21-5p have been reported to be significant diagnostic markers in NSCLC.…”

Section: Mir-4286 Expression Is Upregulated In Nsclc Tissues and Cementioning

confidence: 99%

MicroRNA‐4286 promotes cell proliferation, migration, and invasion via PTEN regulation of the PI3K/Akt pathway in non‐small cell lung cancer

et al. 2019

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It is well‐known that phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor which negatively regulates PI3K/AKT signaling and is activated widely in non‐small cell lung cancers (NSCLC). However, genetic alterations in PTEN genes are rare, suggesting an undefined mechanism(s) for their suppression. Notably, growing evidence indicates that PTEN can be regulated by microRNAs involved in cancer progression. In this study, we discover that the miR‐4286 is overexpressed in NSCLC and negatively regulates the expression of PTEN. Furthermore, we found that miR‐4286 reduces PTEN expression by directly binding to PTEN 3′‐untranslated region (UTR), thereby inhibiting NSCLC cell proliferation and mobility. Moreover, mechanistic investigations revealed that miR‐4286 overexpression was a result of PTEN‐mediated activation of the PI3K/AKT pathway. Taken together, our findings elucidate that miR‐4286 promotes the tumorigenesis of NSCLC by interacting with PTEN. This miR‐4286‐mediated upregulation of PTEN might lead to new therapeutic strategies for NSCLC.

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“…Cell motility was analyzed as previously described . Briefly, for the wound‐healing assay, cells were seeded in six‐well plates 48 h after transfection to form a monolayer.…”

Section: Methodsmentioning

confidence: 99%

The regulation of Neuropilin 1 expression by miR‐338‐3p promotes non‐small cell lung cancer via changes in EGFR signaling

Ding

Zhu

Zeng

et al. 2019

Molecular Carcinogenesis

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Neuropilin 1 (NRP1) is a transmembrane glycoprotein that acts as a co‐receptor for multiple extracellular ligands and typically performs growth‐promoting functions in cancer cells. Accumulating evidence indicates that NRP1 is upregulated, and may be an independent predictor of cancer relapse and poor survival, in many cancer types, including non‐small cell lung cancer (NSCLC). Recent evidence suggests that NRP1 affects tumour cell viability via the epidermal growth factor receptor (EGFR) and Erb‐B2 receptor tyrosine kinase 2 (ErbB2) signalling pathways in venous endothelial cells and in multiple cancer cells. In the present study, we aimed to evaluate the role of NRP1 in NSCLC tumourigenesis and to explore a new post‐transcriptional mechanism of NRP1 regulation via a microRNA that mediates EGFR signalling regulation in lung carcinogenesis. The results showed that miR‐338‐3p is poorly expressed and NRP1 is overexpressed in NSCLC tissues relative to their levels in adjacent noncancerous tissues. Luciferase reporter assays, quantitative real‐time reverse transcription PCR, and Western blot analyses showed that NRP1 is a direct target of miR‐338‐3p. Overexpression of miR‐338‐3p in NSCLC cell lines inhibited cell proliferation in vitro and in vivo. Moreover, cell migration and invasion were inhibited by miR‐338‐3p overexpression. These effects occurred via the EGF signalling pathway. Our data revealed a new post‐transcriptional mechanism by which miR‐338‐3p directly targets NRP1; this mechanism plays a role in enhancing drug sensitivity in EGFR wild‐type patients with NSCLC.

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CD73/NT5E is a target of miR-30a-5p and plays an important role in the pathogenesis of non-small cell lung cancer

Cited by 131 publications

References 44 publications

Predictive value of CD73 expression for the efficacy of immune checkpoint inhibitors in NSCLC

Predictive value of CD73 expression for the efficacy of immune checkpoint inhibitors in NSCLC

MicroRNA‐4286 promotes cell proliferation, migration, and invasion via PTEN regulation of the PI3K/Akt pathway in non‐small cell lung cancer

The regulation of Neuropilin 1 expression by miR‐338‐3p promotes non‐small cell lung cancer via changes in EGFR signaling

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