Dissecting the roles and clinical potential of YY1 in the tumor microenvironment

Yin-Yang 1 (YY1) is a member of the GLI-Kruppel family of zinc finger proteins and plays a vital dual biological role in cancer as an oncogene or a tumor suppressor during tumorigenesis and tumor progression. The tumor microenvironment (TME) is identified as the “soil” of tumor that has a critical role in both tumor growth and metastasis. Many studies have found that YY1 is closely related to the remodeling and regulation of the TME. Herein, we reviewed the expression pattern of YY1 in tumors and summarized the function and mechanism of YY1 in regulating tumor angiogenesis, immune and metabolism. In addition, we discussed the potential value of YY1 in tumor diagnosis and treatment and provided a novel molecular strategy for the clinical diagnosis and treatment of tumors

The Emerging Roles and Clinical Potential of circSMARCA5 in Cancer

Circular RNAs (circRNAs) are a type of endogenous non-coding RNA and a critical epigenetic regulation way that have a closed-loop structure and are highly stable, conserved, and tissue-specific, and they play an important role in the development of many diseases, including tumors, neurological diseases, and cardiovascular diseases. CircSMARCA5 is a circRNA formed by its parental gene SMARCA5 via back splicing which is dysregulated in expression in a variety of tumors and is involved in tumor development with dual functions as an oncogene or tumor suppressor. It not only serves as a competing endogenous RNA (ceRNA) by binding to various miRNAs, but it also interacts with RNA binding protein (RBP), regulating downstream gene expression; it also aids in DNA damage repair by regulating the transcription and expression of its parental gene. This review systematically summarized the expression and characteristics, dual biological functions, and molecular regulatory mechanisms of circSMARCA5 involved in carcinogenesis and tumor progression as well as the potential applications in early diagnosis and gene targeting therapy in tumors

In situ lunar phase curves measured by Chang’E-4 in the Von Kármán Crater, South Pole-Aitken basin

Context. The Yutu-2 rover of the Chang’E-4 (CE-4) mission measured the lunar phase curves in the Von Kármán crater, South Pole-Aitken basin. Aims. We aim to study the photometric properties of the regolith at CE-4’s landing site and compare them with those of Chang’E-3 (CE-3) in order to understand the regolith physical properties of the two landing sites. Methods. We extracted the insitu lunar phase curves measured by CE-4 with a very wide phase angle coverage (1°–144°) and performed photometric model inversions using both the Hapke model and the Lumme-Bowell model. Results. Compared with the CE-3 measurement taken in Mare Imbrium, the CE-4 phase curves show the colorimetric opposition effect and have a steeper and narrower opposition spike. The surface regolith at the CE-4 site is much darker, more porous, more forward scattering, and has a larger slope angle (Hapke model) than that of CE-3. Conclusions. The CE-4 site may have experienced more space weathering alterations than the CE-3 site, which is consistent with their different surface model ages (~3.6 Ga for CE-4 and ~3 Ga for CE-3)

Survival curve of NSUN2 by the Kaplan‒Meier plotter database and PrognoScan database.

(A-B) RFS in READ and SARC cohorts. (C-E) OS in BLCA, PCPG and EACA cohorts. (F) OS in LUAD cohorts. (G-I) OS, RFS and DSS in BRCA cohorts. (J) OS in OV cohorts. (K) DFS in CRC cohorts. OS, overall survival. RFS, relapse-free survival. DSS, disease Specific survival. DFS, disease free survival. (TIF)</p

The subcellular localization and functions of NSUN2 in LIHC, LUAD and HNSC.

(A) The subcellular localization of NSUN2 in HepG2, A549 and 5-8F cells. (B) Detection of the overexpression efficiency of NSUN2 in cell lines. (C) The effect of NSUN2 overexpression on cell proliferation was tested by CCK-8 assay in HepG2, A549 and 5-8F cell lines. (D) The effect of NSUN2 overexpression on cell migration was tested by wound healing assay in HepG2, A549 and 5-8F cell lines. (E) The effect of NSUN2 overexpression on the expression of PD-L1 in HepG2, A549 and 5-8F cell lines.</p

Single-cell analysis of NSUN2.

(A) Expression of NSUN2 in malignant cells, stromal cells, immune cells and functional cells. (B) Scatter plot describing the expression level of NSUN2 in the GSE108989 dataset. (C) Scatter plot describing the expression level of NSUN2 in the GSE98638 dataset.</p

Correlation analysis between NSUN2 and immune subtypes in different cancer types.

(A) In LIHC. (B) In BLCA. (C) In COAD. (D) In BRCA. (E) In LUAD. (F) In KIRC. (G) In KIRP. (H) In GBM. (I) In PAAD. (J) In LGG. (K) In LUSC. (L) In OV. (M) In PCPG. (N) In PRAD. (O) In UCEC. (P) In STAD. C1, wound healing. C2, IFN-γ dominant. C3, inflammatory. C4, lymphocyte depleted. C5, immunologically quiet. C6, TGF-β dominant.</p

Sample number of immune and molecular subtypes.

BackgroundNOP2/Sun RNA methyltransferase 2 (NSUN2), an important methyltransferase of m5C, has been poorly studied in cancers, and the relationship between NSUN2 and immunity remains largely unclear. Therefore, the purpose of this study was to explore the expression and prognostic value of NSUN2 and the role of NSUN2 in immunity in cancers.MethodsThe TIMER, CPTAC and other databases were used to analyze the expression of NSUN2, its correlation with clinical stage and its prognostic value across cancers. Moreover, the TISIDB, TIMER2.0 and Sangerbox platform were used to depict the relationships between NSUN2 and immune molecular subtypes, tumor-infiltrating lymphocytes (TILs), immune checkpoints (ICPs) and immunoregulatory genes. Furthermore, the NSUN2-interacting proteins and related genes as well as the coexpression networks of NSUN2 in LIHC, LUAD and HNSC were explored with the STRING, DAVID, GEPIA2 and LinkedOmics databases. Finally, the subcellular location and function of NSUN2 in HepG2, A549 and 5-8F cells were investigated by performing immunofluorescence, CCK-8 and wound healing assays.ResultsOverall, NSUN2 was highly expressed and related to a poor prognosis in most types of cancers and was also significantly associated with immune molecular subtypes in some cancer types. Furthermore, NSUN2 was significantly associated with the levels of ICPs and immunoregulatory genes. In addition, NSUN2 was found to be involved in a series of immune-related biological processes, such as the humoral immune response in LIHC and LUAD and T-cell activation and B-cell activation in HNSC. Immunofluorescence and CCK-8 assays also confirmed that NSUN2 was widely expressed in the nucleus and cytoplasm, and overexpression of NSUN2 promoted the proliferation and migration of HepG2, A549 and 5-8F cells. NSUN2 was also confirmed to positively regulate the expression of PD-L1.ConclusionNSUN2 serves as a pan-cancer prognostic biomarker and is correlated with the immune infiltration of tumors.</div

Correlation analysis between NSUN2 and molecular subtype in different cancer types.

(A) In LIHC. (B) In HNSC. (C) In BRCA. (D) In ESCA. (E) In OV. (F) In LGG. (G) In ACC. (H) In PCPG. (I) In KIRP. (J) In UCEC. (K) In STAD. (L) In PRAD. (TIF)</p