The Pseudogene <i>Olfr29-ps1</i> Promotes the Suppressive Function and Differentiation of Monocytic MDSCs

Shang, Wencong; Gao, Yuan; Tang, Zilong; Zhang, Yuan; Yang, Rongcun

doi:10.1158/2326-6066.cir-18-0443

Cited by 85 publications

(72 citation statements)

References 45 publications

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“…The tumour-infiltrated MDSC population usually induces antitumour immunity tolerance by inhibiting the proliferation and function of T cells, such as hindering antigen presentation by antigen-presenting cells [36]. Increased METTL3 levels and CD33 + MDSCs have been found in tumour microenvironments and lead to a poor prognosis [37][38][39][40]. In this study, we focused on the distribution of METTL3 and CD33 + MDSCs in the tumour microenvironment of 197 patients with CC.…”

Section: Discussionmentioning

confidence: 99%

Connecting METTL3 and intratumoural CD33+ MDSCs in predicting clinical outcome in cervical cancer

Zhang

Huang

et al. 2020

J Transl Med

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Background Methyltransferase-like 3 (METTL3) is a member of the m6A methyltransferase family and acts as an oncogene in cancers. Recent studies suggest that host innate immunity is regulated by the enzymes controlling m6A epitranscriptomic changes. Here, we aim to explore the associations between the levels of METTL3 and CD33+ myeloid-derived suppressor cells (MDSCs) in tumour tissues and the survival of patients with cervical cancer (CC). Methods Specimens of paraffin embedded tumour from 197 CC patients were collected. The expression levels of METTL3 and CD33 were measured by immunohistochemical (IHC) staining. The clinical associations of the IHC variants were analysed by Pearson’s or Spearman’s chi-square tests. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan–Meier method and log-rank test. Hazard ratios (HRs) and independent significance were obtained via Cox proportional hazards models for multivariate analyses. METTL3 in CD33+ cells or CC-derived cells was knocked down by METTL3-specific siRNA, and MDSC induction in vitro was performed in a co-culture system in the presence of METTL3-siRNA and METTL3-knockdown-CC-derived cells compared with that of the corresponding controls. Results We found that tumour tissues displayed increased levels of METTL3 and CD33+ MDSCs compared with tumour-adjacent tissues from the same CC patients. Importantly, METTL3 expression was positively related to the density of CD33+ cells in tumour tissues (P = 0.011). We further found that the direct CD33+CD11b+HLA-DR− MDSC induction and tumour-derived MDSC induction in vitro were decreased in the absence of METTL3. The level of METTL3 in tumour microenvironments was significantly related to advanced tumour stage. The levels of METTL3 and CD33+ MDSCs in tumour tissues were notably associated with reduced DFS or OS. Cox model analysis revealed that the level of METTL3 in tumour cells was an independent factor for patient survival, specifically for DFS (HR = 3.157, P = 0.022) and OS (HR = 3.271, P = 0.012), while the CD33+ MDSC number was an independent predictor for DFS (HR: 3.958, P = 0.031). Interestingly, in patients with advanced-disease stages (II–IV), METTL3 in tumour cells was an independent factor for DFS (HR = 6.725, P = 0.010) and OS (HR = 5.140, P = 0.021), while CD33+ MDSC density was an independent factor for OS (HR = 8.802, P = 0.037). Conclusion Our findings suggest that CD33+ MDSC expansion is linked to high levels of METTL3 and that METTL3 and CD33+ MDSCs are independent prognostic factors in CC.

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Section: Discussionmentioning

confidence: 99%

Connecting METTL3 and intratumoural CD33+ MDSCs in predicting clinical outcome in cervical cancer

Zhang

Huang

et al. 2020

J Transl Med

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“…Finally, MyD88 is regulated by miR-214-3p, and knocking down MyD88 exerts an important effect on MDSC immunosuppression and differentiation [88]. In conclusion, Olfr29-ps1 relies mainly on the m6A-modified Olfr29-ps1/miR-214-3p/ MyD88 regulatory pathway to modulate MDSC immunosuppression and differentiation [89].…”

Section: Regulation Of Lncrnas By M6a Modificationsmentioning

confidence: 91%

The interplay between m6A RNA methylation and noncoding RNA in cancer

et al. 2019

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N6-methyladenosine (m6A) methylation, one of the most common RNA modifications, has been reported to execute important functions that affect normal life activities and diseases. Most studies have suggested that m6A modification can affect the complexity of cancer progression by regulating biological functions related to cancer. M6A modification of noncoding RNAs regulates the cleavage, transport, stability, and degradation of noncoding RNAs themselves. It also regulates cell proliferation and metastasis, stem cell differentiation, and homeostasis in cancer by affecting the biological function of cells. Interestingly, noncoding RNAs also play significant roles in regulating these m6A modifications. Additionally, it is becoming increasingly clear that m6A and noncoding RNAs potentially contribute to the clinical application of cancer treatment. In this review, we summarize the effect of the interactions between m6A modifications and noncoding RNAs on the biological functions involved in cancer progression. In particular, we discuss the role of m6A and noncoding RNAs as possible potential biomarkers and therapeutic targets in the treatment of cancers.

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“…The tumour-in ltrated MDSC population usually induces antitumour immunity tolerance by inhibiting the proliferation and function of T cells, such as hindering antigen presentation by antigen-presenting cells (36). Increased METTL3 levels and CD33 + MDSCs have been found in tumour microenvironments and lead to a poor prognosis (37)(38)(39)(40). In this study, we focused on the distribution of METTL3 and CD33 + MDSCs in the tumour microenvironment of 197 patients with CC.…”

Section: Discussionmentioning

confidence: 99%

Connecting METTL3 and intratumoural CD33+ MDSCs in predicting clinical outcome in cervical cancer

Zhang

Huang

et al. 2020

Preprint

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Background: Methyltransferase-like 3 (METTL3) is a member of the m6A methyltransferase family and acts as an oncogene in cancers. Recent studies suggest that host innate immunity is regulated by the enzymes controlling m6A epitranscriptomic changes. Here, we aim to explore the associations between the levels of METTL3 and CD33+ myeloid-derived suppressor cells (MDSCs) in tumour tissues and the survival of patients with cervical cancer (CC).Methods: Paraffin tumour specimens from 197 CC patients were collected. The expression levels of METTL3 and CD33 were measured by immunohistochemical (IHC) staining. The clinical associations of the IHC variants were analysed by Pearson's or Spearman's chi-square tests. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan-Meier method and log-rank test. Hazard ratios (HRs) and independent significance were obtained via Cox proportional hazards models for multivariate analyses. METTL3 in CD33+ cells or CC-derived cells was knocked down by METTL3-specific siRNA, and MDSC induction in vitro was performed in a co-culture system in the presence of METTL3-siRNA and METTL3-knockdown-CC-derived cells compared with that of the corresponding controls.Results: We found that tumour tissues displayed increased levels of METTL3 and CD33+ MDSCs compared with tumour-adjacent tissues from the same CC patients. Importantly, METTL3 expression was positively related to the density of CD33+ cells in tumour tissues (P = 0.011). We further found that the direct CD33+CD11b+HLA-DR- MDSC induction and tumour-derived MDSC induction in vitro were decreased in the absence of METTL3. The level of METTL3 in tumour microenvironments was significantly related to advanced tumour stage. The levels of METTL3 and CD33+ MDSCs in tumour tissues were notably associated with reduced DFS or OS. Cox model analysis revealed that the level of METTL3 in tumour cells was an independent factor for patient survival, specifically for DFS (HR = 3.157, P = 0.022) and OS (HR = 3.271, P = 0.012), while the CD33+ MDSC number was an independent predictor for DFS (HR: 3.958, P = 0.031). Interestingly, in patients with advanced-disease stages (II-IV), METTL3 in tumour cells was an independent factor for DFS (HR = 6.725, P= 0.010) and OS (HR = 5.140, P= 0.021), while CD33+ MDSC density was an independent factor for OS (HR = 8.802, P = 0.037).Conclusion: Our findings suggest that CD33+ MDSC expansion is linked to high levels of METTL3 and that METTL3 and CD33+ MDSCs are independent prognostic factors in CC.

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The Pseudogene Olfr29-ps1 Promotes the Suppressive Function and Differentiation of Monocytic MDSCs

Cited by 85 publications

References 45 publications

Connecting METTL3 and intratumoural CD33+ MDSCs in predicting clinical outcome in cervical cancer

Connecting METTL3 and intratumoural CD33+ MDSCs in predicting clinical outcome in cervical cancer

The interplay between m6A RNA methylation and noncoding RNA in cancer

Connecting METTL3 and intratumoural CD33+ MDSCs in predicting clinical outcome in cervical cancer

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