Erratum: RPL32 Promotes Lung Cancer Progression by Facilitating p53 Degradation.

[This corrects the article DOI: 10.1016/j.omtn.2020.05.019.].

Estrogen Receptor Downregulates Expression of PD-1/PD-L1 and Infiltration of CD8+ T Cells by Inhibiting IL-17 Signaling Transduction in Breast Cancer.

Background: The relationship between the interleukin 17 (IL-17) family of cytokines and breast cancer has been widely studied in recent years. Many studies have revealed increased levels of the cytokine IL-17A in estrogen receptor (ER)-negative or triple-negative breast cancer. Upregulation of IL-17A signaling is associated with increased expression of programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) in breast cancer with low ER expression and may elevate the infiltration of CD8+ T cells in tumor tissue. This study aims to determine whether ER downregulates the expression of PD-1/PD-L1, reduces the infiltration of CD8+ T cells, and affects the immune microenvironment by decreasing T-helper 17 (Th17) cell infiltration and inhibiting IL-17 signaling in breast cancer. Methods: Samples in The Cancer Genome Atlas Breast Cancer dataset were grouped by ER status and the PAM50 intrinsic subtype. The expression of IL-17 family cytokines and Th17 cell signature cytokines were compared between groups. IL-17 signaling pathway-related genes that were differentially expressed according to the ER level were identified. The PD-1 and PD-L1 levels were compared between breast cancer samples with different ER statuses and IL-17A/IL-17F expression levels. Correlation analyses of the expression of PD-1/PD-L1 and IL-17 signaling pathway-related genes were performed. The associations of the expression of IL-17 signaling pathway-related genes with the immune microenvironment were investigated. Results: High levels of ER decreased the expression of IL-17A, IL-17C, and IL-17F but increased the expression of IL-17E (IL25), which acts as a suppressor of IL-17 signaling. The expression levels of Th17 cell signature cytokines were significantly increased in ER-negative breast cancer. The expression levels of genes encoding downstream products of IL-17A/IL-17F signaling were downregulated in breast cancer with high ER expression. Increased expression of PD-1/PD-L1 was associated with ER-negative status, IL-17A-positive status, IL-17F-positive status, and upregulation of IL-17 signaling pathway-related genes in breast cancer. Enhanced IL-17 signal transduction was associated with the elevation of CD8+ T cell infiltration and variation of the immune microenvironment of breast cancer. Conclusion: High estrogen receptor levels decrease PD-1/PD-L1 expression and CD8+ T cell infiltration by suppressing Th17 cell infiltration and IL-17 signal transduction in breast cancer.

RPL32 Promotes Lung Cancer Progression by Facilitating p53 Degradation.

Lung cancer is the leading cause of cancer death worldwide, and the overall survival rate of advanced lung cancer patients is unsatisfactory. Ribosomal proteins (RPs) play important roles in carcinogenesis. However, the role of RPL32 in lung cancer has not been demonstrated. Here, we report that RPL32 is aberrantly, highly expressed in lung cancer tissues and that the overexpression of RPL32 is correlated with the poor prognosis of these patients. RPL32 silencing significantly inhibited the proliferation of lung cancer cells, with an observed p53 accumulation and cell-cycle arrest. Mechanistically, knockdown of RPL32 resulted in ribosomal stress and affected rRNA maturation. RPL5 and RPL11 sensed stress and translocated from the nucleus to the nucleoplasm, where they bound to murine double minute 2 (MDM2), an important p53 E3 ubiquitin ligase, which resulted in p53 accumulation and inhibition of cancer cell proliferation. As lung cancer cells usually express high levels of Toll-like receptor 9 (TLR9), we conjugated RPL32 small interfering RNA (siRNA) to the TLR9 ligand CpG to generate CpG-RPL32 siRNA, which could stabilize and guide RPL32 siRNA to lung cancer cells. Excitingly, CpG-RPL32 siRNA displayed strong anticancer abilities in lung cancer xenografts. Therefore, RPL32 is expected to be a potential target for lung cancer treatment.

Selective capture of mesenchymal stem cells over fibroblasts and immune cells on E7-modified collagen substrates under flow circumstances.

Recruitment of endogenous mesenchymal stem cells (MSCs) has become an attractive strategy for in situ tissue regeneration. However, it is of great importance to endow an implant with a specific affinity to MSCs, for many types of cells such as immune cells and fibroblasts can also be recruited. It has been demonstrated that E7 peptides have a specific affinity to MSCs, but their selectivity for MSCs when co-cultured with other cells, especially in flow conditions, has rarely been investigated. In this study, E7-modified collagen substrates were prepared using sulfosuccinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo-SMCC) as the coupling agent. The results of X-ray photoelectron spectroscopy (XPS) and quartz crystal microbalance (QCM) proved that the densities of the immobilized E7 peptides could be modulated by changing the amounts of sulfo-SMCC. The results of cell adhesion rate, adhesion area and adhesion force demonstrated that the immobilization of E7 peptides led to a significant enhancement of the adhesion of bone marrow-derived MSCs (BMSCs) compared to RAW264.7 cells and NIH3T3 cells. The selective adhesion was verified by co-culturing BMSCs with RAW264.7 cells and NIH3T3 cells, which indicated that higher proportions of BMSCs were adhered on the E7-immobilized substrates. By mimicking in vivo flow circumstances, the selective capture of BMSCs by the E7-modified substrates was revealed by a flow model. All these results suggest that E7 immobilization might be a promising strategy for an implant to achieve a better regeneration outcome by enhancing the affinity to the recruited MSCs.