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As one of the most studied ribonucleic acid (RNA) modifications in eukaryotes, N6 -methyladenosine (m6 A) has been shown to play a predominant role in controlling gene expression and influence physiological and pathological processes such as oncogenesis and tumor progression. Writer and eraser proteins, acting opposite to deposit and remove m6 A epigenetic marks, respectively, shape the cellular m6 A landscape, while reader proteins preferentially recognize m6 A modifications and mediate fate decision of the methylated RNAs, including RNA synthesis, splicing, exportation, translation, and stability. Therefore, RNA metabolism in cells is greatly influenced by these three classes of m6 A regulators. Aberrant expression of m6 A regulators has been widely reported in various types of cancer, leading to cancer initiation, progression, and drug resistance. The close links between m6 A and cancer shed light on the potential use of m6 A methylation and its regulators as prognostic biomarkers and drug targets for cancer therapy. Given the notable effects of m6 A in reversing chemoresistance and enhancing immune therapy, it is a promising target for combined therapy. Herein, we summarize the recent discoveries on m6 A and its regulators, emphasizing their influences on RNA metabolism, their dysregulation and impacts in diverse malignancies, and discuss the clinical implications of m6 A modification in cancer.

Background: Sarcomas are heterogeneous rare malignancies constituting approximately 1% of all solid cancers in adults and including more than 70 histological and molecular subtypes with different pathological and clinical development characteristics.\ud \ud Method: We identified prognostic biomarkers of sarcomas by integrating clinical information and RNA-seq data from TCGA and GEO databases. In addition, results obtained from cell cycle, cell migration, and invasion assays were used to assess the capacity for Tanespimycin to inhibit the proliferation and metastasis of sarcoma.\ud \ud Results: Sarcoma samples (N = 536) were divided into four pathological subtypes including DL (dedifferentiated liposarcoma), LMS (leiomyosarcoma), UPS (undifferentiated pleomorphic sarcomas), and MFS (myxofibrosarcoma). RNA-seq expression profile data from the TCGA dataset were used to analyze differentially expressed genes (DEGs) within metastatic and non-metastatic samples of these four sarcoma pathological subtypes with DEGs defined as metastatic-related signatures (MRS). Prognostic analysis of MRS identified a group of genes significantly associated with prognosis in three pathological subtypes: DL, LMS, and UPS. ISG15, NUP50, PTTG1, SERPINE1, and TSR1 were found to be more likely associated with adverse prognosis. We also identified Tanespimycin as a drug exerting inhibitory effects on metastatic LMS subtype and therefore can serve a potential treatment for this type of sarcoma.\ud \ud Conclusions: These results provide new insights into the pathogenesis, diagnosis, treatment, and prognosis of sarcomas and provide new directions for further study of sarcoma.

Directing CO2 conversion using photosynthetic microorganisms offers a promising route to couple CO2 sequestration with petrochemical replacement. However, the low-flux shikimate pathway remains largely unexploited for the synthesis of valuable aromatics. In addition, it is unclear how an enhanced low-flux pathway would influence the photosynthetic chain. We created a powerful metabolic sink by introducing the 2-phenylethanol pathway and an artificial feedback-inhibition-resistant cassette to Synechococcus elongatus. More than 30 % of the fixed carbon was redirected to the shikimate pathway for aromatic synthesis, and carbon fixation and O2 evolution increased significantly. A "self-remodeling" mechanism of the photosynthetic chain was discovered, which accelerates electron transport and reduces energy waste. This study represents a significant step toward the industrial viability of CO2 conversion into aromatic compounds and provides design guidance for improving photosynthetic efficiency.

Irreversible electroporation (IRE) is a physical, non-thermal cancer therapy, which leads to cell death via permanent membrane permeability. This differs from reversible electroporation (RE), which is used to transfer macromolecules into target cells via transient membrane permeability. Given the electrical impedance of the electric field, RE co-exists outside the central zone of IRE ablation. In the present study, the feasibility of using IRE at a therapeutic dose to mediate short hairpin RNA (shRNA) knockdown of human papillomavirus (HPV)18 E6 in HeLa cervical cancer cells in vitro and in vivo was investigated. Experimental results indicated that the HeLa cells survived the combined treatment with IRE and shRNA plasmid transfection. Additionally, residual tumor tissue in a nude mouse model demonstrated green fluorescence. Subsequent studies showed that the combined treatment inhibited the growth of HeLa cells and tumors. Western blotting analysis showed marked changes in the growth-associated proteins between the combined treatment group and the control. It was concluded that a therapeutic dose of IRE was able to mediate the transfection of HPV18 E6 shRNA into HeLa cervical cancer cells in vitro and in vivo. This combined treatment strategy has promising implications in cancer treatment for the ablation of tumors, and in eliminating microscopic residual tumor tissue.