PD-L1 and Immune Infiltration of m6A RNA Methylation Regulators and Its miRNA Regulators in Hepatocellular Carcinoma

Lin, Yubin; Yao, Yinhui; Wang, Ying; Wang, Lingdi; Cui, Haipeng

doi:10.1155/2021/5516100

Cited by 13 publications

(8 citation statements)

References 43 publications

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“…Previous studies have revealed that m6A methylation regulators are associated with RNA translation disorders in cancer occurrence and development [ 24 , 25 ]. However, more and more evidence shows that this process not only occurs in tumors but also occurs in various diseases [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

m6A RNA Methylation Regulators Contribute to Predict and as a Therapy Target of Pulmonary Fibrosis

Deng

Chen

Dongdong

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Pulmonary fibrosis is difficult to treat. Early diagnosis and finding potential drug therapy targets of pulmonary fibrosis are particularly important. There were still various problems with existing pulmonary fibrosis markers, so it is particularly important to find new biomarkers and drug treatment targets. m6A (N6,2′-O-dimethyladenosine) RNA methylation was the cause of many diseases, and it is regulated by m6A methylation regulators. So, whether RNA methylation regulators can be a diagnostic marker and potential drug therapy target of early pulmonary fibrosis needs to be explored. Materials and Methods. Using GSE110147 and GSE33566 in the GEO database to predict the m6A methylation regulators that may be related to the development of pulmonary fibrosis, we used 10 mg/ml bleomycin to induce mouse pulmonary fibrosis models and human pulmonary fibrosis samples, to confirm whether this indicator can be an early diagnostic marker of pulmonary fibrosis. Results. According to the database prediction results, METTL3 can predict the occurrence and development of pulmonary fibrosis, and the results of MASSON and HE staining show that the fibrosis model of mice is successful, and the fibrosis of human samples is obvious. The results of immunohistochemistry showed that the expression of METTL3 was significantly reduced in pulmonary fibrosis. Conclusions. The m6A methylation regulator METTL3 can be considered as an important biomarker for diagnosing pulmonary fibrosis occurrence, furthermore it could be considered as a drug target because of its low expression in pulmonary fibrosis.

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Section: Discussionmentioning

confidence: 99%

m6A RNA Methylation Regulators Contribute to Predict and as a Therapy Target of Pulmonary Fibrosis

Deng

Chen

Dongdong

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…DF2 has the same effect of immune promotion in intrahepatic cholangiocarcinoma (ICC). DF2 directly recognized the m6A 3′UTR region of PD-L1 mRNA and promotes its degradation in an m6A-dependent manner [ 139 ]. DF2 expression enhanced NK cells proliferation, homeostasis, IL-15-mediated survival, and antitumor ability.…”

Section: Yth Domain-containing Proteins Function As M6a Readers In Ca...mentioning

confidence: 99%

Insight into the structure, physiological function, and role in cancer of m6A readers—YTH domain-containing proteins

et al. 2022

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YT521-B homology (YTH) domain-containing proteins (YTHDF1-3, YTHDC1-2) are the most crucial part of N6-methyladenosine (m6A) readers and play a regulatory role in almost all stages of methylated RNA metabolism and the progression of various cancers. Since m6A is identified as an essential post-transcriptional type, YTH domain-containing proteins have played a key role in the m6A sites of RNA. Hence, it is of great significance to study the interaction between YTH family proteins and m6A-modified RNA metabolism and tumor. In this review, their basic structure and physical functions in RNA transcription, splicing, exporting, stability, and degradation as well as protein translation are introduced. Then we discussed the expression regulation of YTH domain-containing proteins in cancers. Furthermore, we introduced the role of the YTH family in cancer biology and systematically demonstrated their functions in various aspects of tumorigenesis and development. To provide a more institute understanding of the role of YTH family proteins in cancers, we summarized their functions and specific mechanisms in various cancer types and presented their involvement in cancer-related signaling pathways.

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“…In pancreatic cancer cells, miR-142-5p inhibits PD-L1 expression and suppressed in vivo tumor growth, suggesting its reinforced expression to potentiate ICPIs treatment [ 77 ]. Interestingly, miR-142-5p influences the tumor microenvironment, PD-L1 expression and HCC prognosis by targeting m 6 A RNA methylation regulators [ 78 ], warranting its validation in advanced HCC undergoing immunotherapy. Beside immunoediting functions, miR-142 also plays a relevant oncogenic role.…”

Section: Micrornas Directly Targeting Pd-l1mentioning

confidence: 99%

MicroRNAs at the Crossroad between Immunoediting and Oncogenic Drivers in Hepatocellular Carcinoma

et al. 2022

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Treatments aimed to reverse the tumor-induced immune tolerance represent a promising approach for advanced hepatocellular carcinoma (HCC). Notwithstanding, primary nonresponse, early, and late disease reactivation still represent major clinical challenges. Here, we focused on microRNAs (miRNAs) acting both as modulators of cancer cell hallmarks and immune system response. We outlined the bidirectional function that some oncogenic miRNAs play in the differentiation and program activation of the immune system development and, at the same time, in the progression of HCC. Indeed, the multifaceted spectrum of miRNA targets allows the modulation of both immune-associated factors and oncogenic or tumor suppressor drivers at the same time. Understanding the molecular changes contributing to disease onset, progression, and resistance to treatments might help to identify possible novel biomarkers for selecting patient subgroups, and to design combined tailored treatments to potentiate antitumor approaches. Preliminary findings seem to argue in favor of a bidirectional function of some miRNAs, which enact an effective modulation of molecular pathways driving oncogenic and immune-skipping phenotypes associated with cancer aggressiveness. The identification of these miRNAs and the characterization of their ‘dual’ role might help to unravel novel biomarkers identifying those patients more likely to respond to immune checkpoint inhibitors and to identify possible therapeutic targets with both antitumor and immunomodulatory functions. In the present review, we will focus on the restricted panel of miRNAs playing a bidirectional role in HCC, influencing oncogenic and immune-related pathways at once. Even though this field is still poorly investigated in HCC, it might represent a source of candidate molecules acting as both biomarkers and therapeutic targets in the setting of immune-based treatments.

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PD-L1 and Immune Infiltration of m6A RNA Methylation Regulators and Its miRNA Regulators in Hepatocellular Carcinoma

Cited by 13 publications

References 43 publications

m6A RNA Methylation Regulators Contribute to Predict and as a Therapy Target of Pulmonary Fibrosis

m6A RNA Methylation Regulators Contribute to Predict and as a Therapy Target of Pulmonary Fibrosis

Insight into the structure, physiological function, and role in cancer of m6A readers—YTH domain-containing proteins

MicroRNAs at the Crossroad between Immunoediting and Oncogenic Drivers in Hepatocellular Carcinoma

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