MicroRNAs (miRNAs) are endogenous, small non-coding RNAs that function in regulation of gene expression. Compelling evidences have demonstrated that miRNA expression is dysregulated in human cancer through various mechanisms, including amplification or deletion of miRNA genes, abnormal transcriptional control of miRNAs, dysregulated epigenetic changes and defects in the miRNA biogenesis machinery. MiRNAs may function as either oncogenes or tumor suppressors under certain conditions. The dysregulated miRNAs have been shown to affect the hallmarks of cancer, including sustaining proliferative signaling, evading growth suppressors, resisting cell death, activating invasion and metastasis, and inducing angiogenesis. An increasing number of studies have identified miRNAs as potential biomarkers for human cancer diagnosis, prognosis and therapeutic targets or tools, which needs further investigation and validation. In this review, we focus on how miRNAs regulate the development of human tumors by acting as tumor suppressors or oncogenes.

Cancer-associated fibroblasts (CAFs) are the predominant components of the tumor microenvironment (TME) and influence cancer hallmarks, but without systematic investigation on their ubiquitous characteristics across different cancer types. Here, we perform pan-cancer analysis on 226 samples across 10 solid cancer types to profile the TME at single-cell resolution, illustrating the commonalities/plasticity of heterogenous CAFs. Activation trajectory of the major CAF types is divided into three states, exhibiting distinct interactions with other cell components, and relating to prognosis of immunotherapy. Moreover, minor CAF components represent the alternative origin from other TME components (e.g., endothelia and macrophages). Particularly, the ubiquitous presentation of endothelial-to-mesenchymal transition CAF, which may interact with proximal SPP1⁺ tumor-associated macrophages, is implicated in endothelial-to-mesenchymal transition and survival stratifications. Our study comprehensively profiles the shared characteristics and dynamics of CAFs, and highlight their heterogeneity and plasticity across different cancer types. Browser of integrated pan-cancer single-cell information is available at https://gist-fgl.github.io/sc-caf-atlas/.

Hepatocellular carcinoma (HCC) is the most frequent subtype of primary liver cancer and one of the leading causes of cancer-related death worldwide. However, the molecular mechanisms underlying HCC pathogenesis have not been fully understood. Emerging evidences have recently suggested the crucial role of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of HCC. Various HCC-related lncRNAs have been shown to possess aberrant expression and participate in cancerous phenotypes (e.g. persistent proliferation, evading apoptosis, accelerated vessel formation and gain of invasive capability) through their binding with DNA, RNA or proteins, or encoding small peptides. Thus, a deeper understanding of lncRNA dysregulation would provide new insights into HCC pathogenesis and novel tools for the early diagnosis and treatment of HCC. In this review, we summarize the dysregulation of lncRNAs expression in HCC and their tumor suppressive or oncogenic roles during HCC tumorigenesis. Moreover, we discuss the diagnostic and therapeutic potentials of lncRNAs in HCC.

Multiple myeloma (MM) is an incurable hematological malignancy. Chimeric antigen receptor (CAR)-expressing T cells have been demonstrated successfully in the clinic to treat B-lymphoid malignancies. However, the potential utility of antigen-specific CAR-engineered natural-killer (NK) cells to treat MM has not been explored. In this study, we determined whether CS1, a surface protein that is highly expressed on MM cells, can be targeted by CAR NK cells to treat MM. We successfully generated a viral construct of a CS1-specific CAR and expressed it in human NK cells. In vitro, CS1-CAR NK cells displayed enhanced MM cytolysis and interferon-γ (IFN-γ) production, and showed a specific CS1-dependent recognition of MM cells. Ex vivo, CS1-CAR NK cells also showed similarly enhanced activities when responding to primary MM tumor cells. More importantly, in an aggressive orthotopic MM xenograft mouse model, adoptive transfer of NK-92 cells expressing CS1-CAR efficiently suppressed the growth of human IM9 MM cells and also significantly prolonged mouse survival. Thus, CS1 represents a viable target for CAR-expressing immune cells, and autologous or allogeneic transplantation of CS1-specific CAR NK cells may be a promising strategy to treat MM.