Abstract RNA modifications have become hot topics recently. By influencing RNA processes, including generation, transportation, function, and metabolization, they act as critical regulators of cell biology. The immune cell abnormality in human diseases is also a research focus and progressing rapidly these years. Studies have demonstrated that RNA modifications participate in the multiple biological processes of immune cells, including development, differentiation, activation, migration, and polarization, thereby modulating the immune responses and are involved in some immune related diseases. In this review, we present existing knowledge of the biological functions and underlying mechanisms of RNA modifications, including N 6 -methyladenosine (m 6 A), 5-methylcytosine (m 5 C), N 1 -methyladenosine (m 1 A), N 7 -methylguanosine (m 7 G), N 4 -acetylcytosine (ac 4 C), pseudouridine (Ψ), uridylation, and adenosine-to-inosine (A-to-I) RNA editing, and summarize their critical roles in immune cell biology. Via regulating the biological processes of immune cells, RNA modifications can participate in the pathogenesis of immune related diseases, such as cancers, infection, inflammatory and autoimmune diseases. We further highlight the challenges and future directions based on the existing knowledge. All in all, this review will provide helpful knowledge as well as novel ideas for the researchers in this area. 

https://www.nature.com/articles/s41392-022-01175-9.pdf

RNA modifications: importance in immune cell biology and related diseases

The roles of N6-methyladenosine methylation in the regulation of bone development, bone remodeling and osteoporosis.

Abstract It is well known that noncoding RNAs (ncRNAs) cannot encode proteins, but they can play important regulatory roles in tumors by combining with proteins, RNAs, and DNAs. As more and more studies reveal the important roles and underlying mechanisms of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in cancer, their huge application potential in cancer therapy cannot be ignored. For example, lncRNAs can be involved in tumor‐related signal transduction pathways, cell cycle control, DNA damage, epigenetic regulation, and microRNA control. A group of studies confirmed that abnormal expression of lncRNAs can affect cancer progression. Furthermore, as covalently closed continuous circular ncRNAs, many recent studies have shown that circRNAs have regulatory effects and other important biological significances in cancer. Interestingly, circRNAs were found to have translational functions. This has greatly attracted people's attention to circRNAs research. In this review, we introduce the important roles of lncRNAs and circRNAs in some representative cancers, respectively. Furthermore, we focus on the biological functions and important clinical therapeutic implications of lnRNAs and circRNAs in neuroblastoma. Our review also focuses on providing rationale and relevant references for novel biomarkers for neuroblastoma diagnosis, prognosis, and treatment.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/mco2.141

LncRNAs and CircRNAs in cancer

ABSTRACT Emerging evidence has emphasized the critical roles played by N6-methyladenosine RNA (m6A) modification in colorectal carcinoma (CRC) initiation and progression. However, the roles and mechanism of m6A and KIAA1429 in CRC progression require further clarification. Here, our research aimed to investigate the functions of KIAA1429 in CRC tumorigenesis. Results indicated that KIAA1429 up-regulation closely correlated to the poor prognosis of CRC patients. Bio-functional assays demonstrated that KIAA1429 promoted the aerobic glycolysis, including glucose uptake, lactate production, ATP generation and extracellular acidification rate (ECAR). Mechanistically, KIAA1429 positively up-regulated HK2 level via increasing its mRNA stability by binding the m6A site of HK2 mRNA via m6A-independent manner. Collectively, our work indicates that KIAA1429 has the potential to promote CRC carcinogenesis by targeting HK2 via m6A-independent manner, providing insight into the critical roles of m6A in CRC. Graphical abstract

https://www.tandfonline.com/doi/pdf/10.1080/21655979.2022.2065952?needAccess=true

N6-methyladenosine methyltransferase KIAA1429 elevates colorectal cancer aerobic glycolysis via HK2-dependent manner

Abstract Gastrointestinal cancer is the most common human malignancy characterized by high lethality and poor prognosis. Emerging evidences indicate that N6-methyladenosine (m6A), the most abundant post-transcriptional modification in eukaryotes, exerts important roles in regulating mRNA metabolism including stability, decay, splicing, transport, and translation. As the key component of the m6A methyltransferase complex, methyltransferase-like 14 (METTL14) catalyzes m6A methylation on mRNA or non-coding RNA to regulate gene expression and cell phenotypes. Dysregulation of METTL14 was deemed to be involved in various aspects of gastrointestinal cancer, such as tumorigenesis, progression, chemoresistance, and metastasis. Plenty of findings have opened up new avenues for exploring the therapeutic potential of gastrointestinal cancer targeting METTL14. In this review, we systematically summarize the recent advances regarding the biological functions of METTL14 in gastrointestinal cancer, discuss its potential clinical applications and propose the research forecast. 

/pdf/the-role-mechanism-and-application-of-rna-methyltransferase-2bqqe36w.pdf

The role, mechanism, and application of RNA methyltransferase METTL14 in gastrointestinal cancer

RNA modification plays a crucial role in many biological functions, and its abnormal regulation is associated with the progression of cancer. Among them, N6-methyladenine (m6A) is the most abundant RNA modification. Methyltransferase-like 14 (METTL14) is the central component of the m6A methylated transferase complex, which is involved in the dynamic reversible process of m6A modification. METTL14 acts as both an oncogene and tumor suppressor gene to regulate the occurrence and development of various cancers. The abnormal m6A level induced by METTL14 is related to tumorigenesis, proliferation, metastasis, and invasion. To date, the molecular mechanism of METTL14 in various malignant tumors has not been fully studied. In this paper, we systematically summarize the latest research progress on METTL14 as a new biomarker for cancer diagnosis and its biological function in human tumors and discuss its potential clinical application. This study aims to provide new ideas for targeted therapy and improved prognoses in cancer. 

/pdf/functions-mechanisms-and-therapeutic-implications-of-mettl14-k717c327.pdf

Functions, mechanisms, and therapeutic implications of METTL14 in human cancer

Role of N7-methylguanosine (m7G) in cancer.

With the development of RNA modification research, the importance of N6-methyladenosine (m6A) in tumors cannot be ignored. m6A promotes the self-renewal of tumor stem cells and the proliferation of tumor cells. It affects post-transcriptional gene expression through epigenetic mechanisms, combining various factors to determine proteins' fate and altering the biological function. This modification process runs through the entire tumors, and genes affected by m6A modification may be the critical targets for cancers breakthroughs. Though generally less dangerous than adult cancer, pediatric cancer accounts for a significant proportion of child deaths. What is more alarming is that the occurrences of adult tumors are highly associated with the poor prognoses of pediatric tumors. Therefore, it is necessary to pay attention to the importance of pediatric cancer and discover new therapeutic targets, which will help improve the therapeutic effect and prognoses of the diseases. We collected and investigated m6A modification in pediatric cancers based on mRNA and non-coding RNA, finding that m6A factors were involved in glioma, hepatoblastoma, nephroblastoma, neuroblastoma, osteosarcoma, medulloblastoma, retinoblastoma, and acute lymphoblastic leukemia. Consequently, we summarized the relationships between the m6A factors and these pediatric cancers. 

The role of m6A modification in pediatric cancer.

Because of dismal prognosis in gastric cancer, identifying relevant prognostic factors is necessary. Phosphoserine phosphatase (PSPH) exhibits different expression patterns in many cancers and has been reported to affect the prognosis of patients with cancer. In this study, we examined the prognostic role of metabolic gene PSPH in gastric cancer based on the TCGA dataset and our hospital-based cohort cases.We collected and analysed RNA-seq data of Pan-cancer and gastric cancer in the TCGA dataset and PSPH expression data obtained from immunohistochemical analysis of 243 patients with gastric cancer from Sun Yat-sen University cancer center. Further, Kaplan-Meier survival analysis and Cox analysis were used to assess the effect of PSPH on prognosis. The ESTIMATE and Cibersort algorithms were used to elucidate the relationship between PSPH and the abundance of immune cells using the TCGA dataset.We observed that PSPH expression displayed considerably high in gastric cancer and it was significantly associated with inferior prognosis (P = 0.043). Surprisingly, there was a significant relationship between lower immune scores and high expression of PSPH (P < 0.05). Furthermore, patients with a low amount of immune cells exhibited poor prognosis (P = 0.046). The expression of PSPH significantly increased in activated memory CD4 T cells, resting NK cells and M0 macrophages (P = 0.037, < 0.001, and 0.005, respectively).This study highlighted that PSPH influences the prognosis of patients with gastric cancer, and this is associated with the infiltration of tumour immune cells, indicating that PSPH may be a new immune-related target for treating gastric cancer. 

/pdf/phosphoserine-phosphatase-as-a-prognostic-biomarker-in-gz8zu51l.pdf

Lei Miao

Papers

Functions, mechanisms, and therapeutic implications of METTL14 in human cancer

Role of N7-methylguanosine (m7G) in cancer.

The role of m6A modification in pediatric cancer.

LncRNAs and CircRNAs in cancer

Phosphoserine phosphatase as a prognostic biomarker in patients with gastric cancer and its potential association with immune cells