Evasion of immune system is a hallmark of cancer, which enables cancer cells to escape the attack from immune cells. Cancer cells can express many immune inhibitory signalling proteins to cause immune cell dysfunction and apoptosis. One of these inhibitory molecules is programmed death-ligand-1 (PD-L1), which binds to programmed death-1 (PD-1) expressed on T-cells, B-cells, dendritic cells and natural killer T-cells to suppress anti-cancer immunity. Therefore, anti-PD-L1 and anti-PD-1 antibodies have been used for the treatment of cancer, showing promising outcomes. However, only a proportion of patients respond to the treatments. Further understanding of the regulation of PD-L1 expression could be helpful for the improvement of anti-PD-L1 and anti-PD-1 treatments. Studies have shown that PD-L1 expression is regulated by signalling pathways, transcriptional factors and epigenetic factors. In this review, we summarise the recent progress of the regulation of PD-L1 expression in cancer cells and propose a regulatory model for unified explanation. Both PI3K and MAPK pathways are involved in PD-L1 regulation but the downstream molecules that control PD-L1 and cell proliferation may differ. Transcriptional factors hypoxia-inducible factor-1α and signal transducer and activation of transcription-3 act on the promoter of PD-L1 to regulate its expression. In addition, microRNAs including miR-570, miR-513, miR-197, miR-34a and miR-200 negatively regulate PD-L1. Clinically, it could increase treatment efficacy of targeted therapy by choosing those molecules that control both PD-L1 expression and cell proliferation.

A lysosome-specific and two-photon fluorescent probe, Lyso-NINO, demonstrates high selectivity and sensitivity toward NO, lower cytotoxicity, and perfect lysosomal localization. With the aid of Lyso-NINO, the first capture of NO within lysosomes of macrophage cells has been achieved using both two-photon fluorescence microscopy and flow cytometry.

The list of long non-coding RNAs (lncRNAs) involved in the p53 pathway of the DNA damage response is rapidly expanding, but whether lncRNAs have a role in maintaining the de novo structure of DNA is unknown. Here, we demonstrate that the p53-responsive lncRNA GUARDIN is important for maintaining genomic integrity under steady-state conditions and after exposure to exogenous genotoxic stress. GUARDIN is necessary for preventing chromosome end-to-end fusion through maintaining the expression of telomeric repeat-binding factor 2 (TRF2) by sequestering microRNA-23a. Moreover, GUARDIN also sustains breast cancer 1 (BRCA1) stability by acting as an RNA scaffold to facilitate the heterodimerization of BRCA1 and BRCA1-associated RING domain protein 1 (BARD1). As such, GUARDIN silencing triggered apoptosis and senescence, enhanced cytotoxicity of additional genotoxic stress and inhibited cancer xenograft growth. Thus, GUARDIN may constitute a target for cancer treatment.

Past studies have shown that amplified insulin-like growth factor 1 (IGF1)/IGF1 receptor (IGF1-R) signalling has an important role in colorectal cancer (CRC) development, progression and resistance to treatment. In this report, we demonstrate that downregulation of microRNA-497 (miR-497) as a result of DNA copy number reduction is involved in upregulation of IGF1-R in CRC cells. MiR-497 and miR-195 of the miR-15/16/195/424/497 family that share the same 3′ untranslated region (3′UTR) binding seed sequence and are predicted to target IGF1-R were concurrently downregulated in the majority of CRC tissues relative to paired adjacent normal mucosa. However, only overexpression of miR-497 led to suppression of the IGF1-R 3′UTR activity and downregulation of the endogenous IGF1-R protein in CRC cells. This was associated with inhibition of cell survival, proliferation and invasion, and increased sensitivity to apoptosis induced by various stimuli including the chemotherapeutic drugs cisplatin and 5-fluorouracil, and the death ligand tumour necrosis factor-related apoptosis-inducing ligand. The biological effect of miR-497 on CRC cells was largely mediated by inhibition of phosphatidylinositol 3-kinase/Akt signalling, as overexpression of an active form of Akt reversed its impact on cell survival and proliferation, recapitulating the effect of overexpression of IGF1-R. Downregulation of miR-497 and miR-195 appeared to associate with copy number loss of a segment of chromosome 17p13.1, where these miRs are located at proximity. Similarly to miR-195, the members of the same miR family, miR-424 that was upregulated, and miR-15a, miR-15b and miR-16 that were unaltered in expression in CRC tissues compared with paired adjacent normal mucosa, did not appear to have a role in regulating the expression of IGF1-R. Taken together, these results identify downregulation of miR-497 as an important mechanism of upregulation of IGF1-R in CRC cells that contributes to malignancy of CRC.