Epigenetics including DNA and RNA modifications have always been the hotspot field of life sciences in the post-genome era. Since the first mapping of N6-methyladenosine (m⁶A) and the discovery of its widespread presence in mRNA, there are at least 160-170 RNA modifications have been discovered. These methylations occur in different RNA types, and their distribution is species-specific. 5-methylcytosine (m⁵C) has been found in mRNA, rRNA and tRNA of representative organisms from all kinds of species. As reversible epigenetic modifications, m⁵C modifications of RNA affect the fate of the modified RNA molecules and play important roles in various biological processes including RNA stability control, protein synthesis, and transcriptional regulation. Furthermore, accumulative evidence also implicates the role of RNA m⁵C in tumorigenesis. Here, we review the latest progresses in the biological roles of m⁵C modifications and how it is regulated by corresponding “writers”, “readers” and “erasers” proteins, as well as the potential molecular mechanism in tumorigenesis and cancer immunotherapy.

Background: The use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) brings remarkable benefits for the survival of patients with advanced NSCLC harboring EGFR mutations. Unfortunately, acquired resistance seems to be inevitable and limits the application of EGFR-TKIs in clinical practice. This study reported a common molecular mechanism sustaining resistance and potential treatment options to overcome EGFR-TKIs resistance.Methods: EGFR-TKIs resistant NSCLC cells were established and confirmed by MTT assay. Cholesterol content was detected and the promotional function of cholesterol on NSCLC growth was determined in vivo. Then, we identified ERRα expression as the downstream factor of cholesterol-mediated drug resistance. To dissect the regulatory mechanism, we conducted experiments, including immunofluorescence, co-immunoprecipitation, luciferase reporter assay and chromatin immunoprecipitation assay.Results: Long-term exposure to EGFR-TKIs generate drug resistance with the characteristic of cholesterol accumulation in lipid rafts, which promotes EGFR and Src to interact and lead EGFR/Src/Erk signaling reactivation-mediated SP1 nuclear translocation and ERRα re-expression. Further investigation identifies ERRα as a target gene of SP1. Functionally, re-expression of ERRα sustains cell proliferation by regulating ROS detoxification process. Lovastatin, a drug used to decrease cholesterol level, and XCT790, an inverse agonist of ERRα, overcome gefitinib and osimertinib resistance both in vitro and in vivo.Conclusions: Our study indicates that cholesterol/EGFR/Src/Erk/SP1 axis-induced ERRα re-expression promotes survival of gefitinib and osimertinib-resistant cancer cells. Besides, we demonstrate the potential of lowing cholesterol and downregulation of ERRα as effective adjuvant treatment of NSCLC.

The inherent heterogeneity of individual cells in cell populations plays significant roles in disease development and progression, which is critical for disease diagnosis and treatment. Substantial evidences show that the majority of traditional gene profiling methods mask the difference of individual cells. Single cell sequencing can provide data to characterize the inherent heterogeneity of individual cells, and reveal complex and rare cell populations. Different microfluidic technologies have emerged for single cell researches and become the frontiers and hot topics over the past decade. In this review article, we introduce the processes of single cell sequencing, and review the principles of microfluidics for single cell analysis. Also, we discuss the common high-throughput single cell sequencing technologies along with their advantages and disadvantages. Lastly, microfluidics applications in single cell sequencing technology for the diagnosis of cancers and immune system diseases are briefly illustrated.

Cell-free DNA (cfDNA) is easily accessible in peripheral blood and can be used as biomarkers for cancer diagnostics, prognostics, and therapeutics. The applications of cfDNA in various areas of cancer management are attracting attention. In this review article, we discuss the potential relevance of using cfDNA analysis in clinical oncology, particularly in cancer screening, early diagnosis, therapeutic evaluation, monitoring disease progression; and determining disease prognosis.

Cancer stem cells (CSCs), the subpopulation of cancer cells, have the capability of proliferation, self-renewal, and differentiation. The presence of CSCs is a key factor leading to tumor progression and metastasis. Extracellular vesicles (EVs) are nano-sized particles released by different kinds of cells and have the capacity to deliver certain cargoes, such as nucleic acids, proteins, and lipids, which have been recognized as a vital mediator in cell-to-cell communication. Recently, more and more studies have reported that EVs shed by CSCs make a significant contribution to tumor progression. CSCs-derived EVs are involved in tumor resistance, metastasis, angiogenesis, as well as the maintenance of stemness phenotype and tumor immunosuppression microenvironment. Here, we summarized the molecular mechanism by which CSCs-derived EVs in tumor progression. We believed that the fully understanding of the roles of CSCs-derived EVs in tumor development will definitely provide new ideas for CSCs-based therapeutic strategies.