microRNA 125a Regulates MHC-I Expression on Esophageal Adenocarcinoma Cells, Associated With Suppression of Antitumor Immune Response and Poor Outcomes of Patients

Mari, Luigi; Hoefnagel, Sanne; Zito, Domenico; Meent, Marian van de; Endert, Peter Van; Calpe, Silvia; Serra, Maria del Carmen Sancho; Heemskerk, Mirjam H.M.; Laarhoven, Hanneke W. M. van; Hulshof, Maarten C.C.M.; Gisbertz, Suzanne S.; Medema, Jan Paul; Henegouwen, Mark I. van Berge; Meijer, Sybren L.; Bergman, Jacques; Milano, Francesca; Krishnadath, Kausilia K.

doi:10.1053/j.gastro.2018.06.030

Cited by 73 publications

(62 citation statements)

References 34 publications

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“…10 Additionally, according to the previous studies that miR-125a overexpression reduced the various kinds of cell proliferation, such as endothelial cells and adipocytes, psoriatic patients with miR-125a overexpression may experience reduced epidermal cell proliferation and epidermal hyperplasia; thus, miR-125a overexpression was associated with less risk of psoriasis. 14,23,24 In our present study, we found that baseline miR-125a expression was lower in PASI-75 responders compared with PASI-75 non-responders, and logistic regression model analysis exhibited that miR-125a was an independent predictive factor for worse PASI-75 response to ETN at M6 in psoriatic patients. miRNA-125a is also reported to serve as a potential prognostic biomarker in autoimmune and inflammatory diseases.…”

Section: Discussionsupporting

confidence: 60%

“…Thus, we speculated that miR-125a expression may present potential for predicting response to ETN treatment in psoriatic patients. 14,23,24 In our present study, we found that baseline miR-125a expression was lower in PASI-75 responders compared with PASI-75 non-responders, and logistic regression model analysis exhibited that miR-125a was an independent predictive factor for worse PASI-75 response to ETN at M6 in psoriatic patients. The possible reasons may include that miR-125a was negatively associated with disease severity in psoriatic patients, and psoriatic patients with high disease severity had more of a gap in the decrease of PASI score and achieved PASI-75 response more easily compared with those with low disease severity; therefore, miR-125a expression was negatively associated with PASI-75 response at M6.…”

Section: Discussionsupporting

confidence: 60%

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Measurement of circulating miRNA‐125a exhibits good value in the management of etanercept‐treated psoriatic patients

Pei

Cao

Qin

et al. 2019

The Journal of Dermatology

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This study aimed to explore the correlation of miR-125a with risk and severity of psoriasis, and further investigate the potential of miR-125a for predicting response to etanercept (ETN) treatment in psoriatic patients. Moderate to severe plaque psoriatic patients (n = 126) about to undergo ETN treatment for 6 months were recruited. Their plasma samples were obtained, and Psoriasis Area and Severity Index (PASI) scores and PASI-75 response rate were assessed at baseline (M0), and at 1 (M1), 3 (M3) and 6 months (M6) of treatment. Referring to PASI-75 response status at M6, patients were categorized as PASI-75 responders and PASI-75 non-responders. Healthy controls (HC, n =120) were also enrolled and their plasma samples were collected. In addition, plasma miR-125a was determined by quantitative polymerase chain reaction. miR-125a was decreased in psoriatic patients compared with HC; further, the receiver-operator curve (ROC) exhibited that miR-125a was of good value in differentiating psoriatic patients from HC with an area under the curve (AUC) of 0.802. In psoriatic patients, miR-125a was negatively associated with PASI score to some extent. Interestingly, baseline miR-125a was lower in PASI-75 responders than PASI-75 non-responders; further, ROC showed it predicted PASI-75 response at M6 to some extent with AUC of 0.672. Multivariate logistic regression also revealed that miR-125a was an independent predictive factor for worse PASI-75 response at M6. Furthermore, miR-125a expression was gradually increased during the treatment in PASI-75 responders, but unchanged in PASI-75 non-responders. Measurement of circulating miR-125a exhibits good value in the management of ETN-treated psoriatic patients.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionsupporting

confidence: 60%

Measurement of circulating miRNA‐125a exhibits good value in the management of etanercept‐treated psoriatic patients

Pei

Cao

Qin

et al. 2019

The Journal of Dermatology

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Section: The Role Of Mirnas In Cancer Immune Evasionmentioning

confidence: 82%

“…Similarly, in esophageal adenocarcinoma cells, it has been verified that miR-125a-5p could bind to the 3′-UTR of TAP2 mRNA [54]. Also, it was detected that the 3′-UTR of HLA-A, HLA-B, and HLA-C mRNAs had the binding site for miR-148a-3p [54]. Meantime, the results of proteomic screening suggested that miR-27a promoted cancer progression by decreasing MHC-I expression on cell surface, inhibiting T cell infiltration and cytotoxic activities [56].…”

Section: The Role Of Mirnas In Cancer Immune Evasionmentioning

confidence: 90%

The role of cancer-derived microRNAs in cancer immune escape

et al. 2020

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During malignant transformation, accumulated somatic mutations endow cancer cells with increased invasiveness and immunogenicity. Under selective pressure, these highly immunogenic cancer cells develop multiple strategies to evade immune attack. It has been well established that cancer cells could downregulate the expression of major histocompatibility complex, acquire alterations in interferon pathway, and upregulate the activities of immune checkpoint pathways. Besides, cancer cells secret numerous cytokines, exosomes, and microvesicles to regulate the functions and abundances of components in the tumor microenvironment including immune effector cells and professional antigen presentation cells. As the vital determinant of post-transcriptional regulation, microRNAs (miRNAs) not only participate in cancer initiation and progression but also regulate anti-cancer immune response. For instance, some miRNAs affect cancer immune surveillance and immune escape by interfering the expression of immune attack-associated molecules. A growing body of evidence indicated that cancer-derived immune modulatory miRNAs might be promising targets to counteract cancer immune escape. In this review, we summarized the role of some miRNAs in cancer immune escape and discussed their potential clinical application as treatment targets.

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“…miR-19a upregulation in asthma is an indicator and a cause of increased T H 2 cytokine production in the airways [6]. Moreover, the expression of interferon-regulated genes and MHC class I molecules are modulated by microRNAs, such as miR-9 [12], miR-125a [13], miR-520b [14], let-7f-5p [15], let-7i-5p [15], miR-146b-5p [15] and miR-185-5p [15]. Our findings and published reports strongly indicate a novel role of miR-19 in linking inflammation and cancer, which remains to be fully characterized.…”

Section: Introductionmentioning

confidence: 99%

miR-19 regulates the expression of interferon-induced genes and MHC class I genes in human cancer cells

Lin

Chen

et al. 2020

Int. J. Med. Sci.

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MicroRNA -19 (miR-19) is identified as the key oncogenic component of the miR-17-92 cluster. When we explored the functions of the dysregulated miR-19 in lung cancer, microarray-based data unexpectedly demonstrated that some immune and inflammatory response genes (i.e., IL32, IFI6 and IFIT1) were generally down-regulated by miR-19 overexpression in A549 cells, which prompted us to fully investigate whether the miR-19 family (i.e., miR-19a and miR-19b-1) was implicated in regulating the expression of immune and inflammatory response genes in cancer cells. In the present study, we observed that miR-19a or miR-19b-1 overexpression by miRNA mimics in the A549, HCC827 and CNE2 cells significantly downregulated the expression of interferon (IFN)-regulated genes (i.e., IRF7, IFI6, IFIT1, IFITM1, IFI27 and IFI44L). Furthermore, the ectopic miR-19a or miR-19b-1 expression in the A549, HCC827, CNE2 and HONE1 cells led to a general downward trend in the expression profile of major histocompatibility complex (MHC) class I genes (such as HLA-B, HLA-E, HLA-F or HLA-G); conversely, miR-19a or miR-19b-1 inhibition by the miRNA inhibitor upregulated the aforementioned MHC Class I gene expression, suggesting that miR-19a or miR-19b-1 negatively modulates MHC Class I gene expression. The miR-19a or miR-19b-1 mimics reduced the expression of interleukin (IL)-related genes (i.e., IL1B, IL11RA and IL6) in the A549, HCC827, CNE2 or HONE1 cells. The ectopic expression of miR-19a or miR-19b-1 downregulated IL32 expression in the A549 and HCC827 cells and upregulated IL32 expression in CNE2 and HONE1 cells. In addition, enforced miR-19a or miR-19b-1 expression suppressed IL-6 production by lung cancer and nasopharyngeal carcinoma (NPC) cells. Taken together, these findings demonstrate, for the first time, that miR-19 can modulate the expression of IFN-induced genes and MHC class I genes in human cancer cells, suggesting a novel role of miR-19 in linking inflammation and cancer, which remains to be fully characterized.

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microRNA 125a Regulates MHC-I Expression on Esophageal Adenocarcinoma Cells, Associated With Suppression of Antitumor Immune Response and Poor Outcomes of Patients

Cited by 73 publications

References 34 publications

Measurement of circulating miRNA‐125a exhibits good value in the management of etanercept‐treated psoriatic patients

Measurement of circulating miRNA‐125a exhibits good value in the management of etanercept‐treated psoriatic patients

The role of cancer-derived microRNAs in cancer immune escape

miR-19 regulates the expression of interferon-induced genes and MHC class I genes in human cancer cells

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