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The tumor necrosis factor (TNF) receptor RANK (TNFRSF11A) and its ligand RANKL (TNFSF11) regulate osteoclast development and bone metabolism. They also control stem cell expansion and proliferation of mammary epithelial cells via the sex hormone progesterone. As such, RANKL and RANK have been implicated in the onset of hormone-induced breast cancer. Recently, RANK/RANKL were identified as crucial regulators for BRCA1 mutation-driven breast cancer. Current prevention strategies for BRCA1 mutation carriers are associated with wide-ranging risks; therefore, the search for alternative, non-invasive strategies is of paramount importance. We summarize here the functions of the RANKL/RANK pathway in mammalian physiology and focus on its recently uncovered role in breast cancer. We propose that anti-RANKL therapy should be pursued as a preventative strategy for breast cancer. [ABSTRACT FROM AUTHOR]

Abstract: The global outbreak in 2002–2003 of severe acute respiratory syndrome (SARS) posed a serious threat to public health and had a significant impact on socioeconomic stability. Although the global outbreak of SARS has been contained, there are serious concerns over its re-emergence and bioterrorism potential, and up to date, no specific treatment exists for this disease. Here we review the progress of studies on the pathogenesis of the disease, in particular, studies on the molecular level. [Copyright &y& Elsevier]

Background: Lung cancer remains the foremost reason of cancer‐related mortality, with invasion and metastasis profoundly influencing patient prognosis. N‐acetyltransferase 10 (NAT10) catalyzes the exclusive N (4)‐acetylcytidine (ac4C) modification in eukaryotic RNA. NAT10 dysregulation is linked to various diseases, yet its role in non‐small cell lung cancer (NSCLC) invasion and metastasis remains unclear. Our study delves into the clinical significance and functional aspects of NAT10 in NSCLC. Methods: We investigated NAT10's clinical relevance using The Cancer Genome Atlas (TCGA) and a group of 98 NSCLC patients. Employing WB, qRT‐PCR, and IHC analyses, we assessed NAT10 expression in NSCLC tissues, bronchial epithelial cells (BECs), NSCLC cell lines, and mouse xenografts. Further, knockdown and overexpression techniques (siRNA, shRNA, and plasmid) were employed to evaluate NAT10's effects. A series of assays were carried out, including CCK‐8, colony formation, wound healing, and transwell assays, to elucidate NAT10's role in proliferation, invasion, and metastasis. Additionally, we utilized lung cancer patient‐derived 3D organoids, mouse xenograft models, and Remodelin (NAT10 inhibitor) to corroborate these findings. Results: Our investigations revealed high NAT10 expression in NSCLC tissues, cell lines and mouse xenograft models. High NAT10 level correlated with advanced T stage, lymph node metastasis and poor overall survive. NAT10 knockdown curtailed proliferation, invasion, and migration, whereas NAT10 overexpression yielded contrary effects. Furthermore, diminished NAT10 levels correlated with increased E‐cadherin level whereas decreased N‐cadherin and vimentin expressions, while heightened NAT10 expression displayed contrasting results. Notably, Remodelin efficiently attenuated NSCLC proliferation, invasion, and migration by inhibiting NAT10 through the epithelial‐mesenchymal transition (EMT) pathway. Conclusions: Our data underscore NAT10 as a potential therapeutic target for NSCLC, presenting avenues for targeted intervention against lung cancer through NAT10 inhibition. [ABSTRACT FROM AUTHOR]

Long noncoding ribonucleic acids (RNAs; LncRNAs) endowed with both protein-coding and noncoding functions are referred to as 'dual functional lncRNAs'. Recently, dual functional lncRNAs have been intensively studied and identified as involved in various fundamental cellular processes. However, apart from time-consuming and cell-type-specific experiments, there is virtually no in silico method for predicting the identity of dual functional lncRNAs. Here, we developed a deep-learning model with a multi-head self-attention mechanism, LncReader, to identify dual functional lncRNAs. Our data demonstrated that LncReader showed multiple advantages compared to various classical machine learning methods using benchmark datasets from our previously reported cncRNAdb project. Moreover, to obtain independent in-house datasets for robust testing, mass spectrometry proteomics combined with RNA-seq and Ribo-seq were applied in four leukaemia cell lines, which further confirmed that LncReader achieved the best performance compared to other tools. Therefore, LncReader provides an accurate and practical tool that enables fast dual functional lncRNA identification. [ABSTRACT FROM AUTHOR]

Background: Esophageal carcinoma is one of the most fatal cancers worldwide. In China, over 90% of esophageal cancer patients are diagnosed with esophageal squamous cell carcinoma (ESCC). Currently, the survival and prognosis of ESCC patients are not satisfying because of insufficient early screening and lack of efficacious medication. Accumulating studies have suggested that antibody‐drug conjugates (ADC) represent a promising antitumor strategy. Method: Here, we carried out a specific membrane proteome screening with ESCC patients' samples using a high‐throughput antibody microarray to uncover potential targets for ADC development. Candidates were validated with expression and cytotoxicity evaluation both in vitro and in vivo. Results: Our data have shown that the Piezo‐Type Mechanosensitive Ion Channel Component 1 (PIEZO1) is particularly overexpressed in human ESCC tumors and can be efficiently internalized when bound with its monoclonal antibody. Furthermore, the PIEZO1 antibody combined with monomethyl auristatin E (MMAE) can specifically kill PIEZO1 high‐expressed ESCC tumor cells by inducing cell cycle arrest and apoptosis. More importantly, the Anti‐PIEZO1‐MMAE can significantly suppress tumor progression in ESCC xenograft tumor models without any obvious side effects. Conclusion: Taken together, our work demonstrates that PIEZO1 is a promising target to develop ADCs for human ESCC treatment, providing a new strategy for ESCC patients' personalized therapy. [ABSTRACT FROM AUTHOR]

Aerobic exercise is well recognized to be beneficial to physical and mental health. Many studies have shown that aerobic exercise can improve the human immune system, but whether it could affect lung regeneration and inflammation remained unclear. Bronchioloalveolar stem cells (BASCs) play a key role in lung regeneration and repair, but it is unclear whether aerobic exercise affects BASCs. Here, we randomly divided 8 weeks old male mice into three groups: the control group without any aerobic exercise; the rest group which received 2 weeks of aerobic exercise (running wheel training) plus 5 days' rest, and the exercise group which received 2 weeks of aerobic exercise without any rest. Our data indicated that mice in the exercise group had significantly increased BASCs compared to the control group, such difference did not exist in the rest group. Furthermore, the immune profiling suggested that lung inflammation was slightly up-regulated in the exercise group, particularly the inflammatory monocytes and IL-17A+ T cells. In conclusion, we provide direct evidence showing that aerobic exercise can facilitate lung regeneration with mild inflammatory effect, this finding is of great importance in the current COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Summary Caloric restriction mimetics (CRMs) mimic the biochemical effects of nutrient deprivation by reducing lysine acetylation of cellular proteins, thus triggering autophagy. Treatment with the CRM hydroxycitrate, an inhibitor of ATP citrate lyase, induced the depletion of regulatory T cells (which dampen anticancer immunity) from autophagy-competent, but not autophagy-deficient, mutant KRAS-induced lung cancers in mice, thereby improving anticancer immunosurveillance and reducing tumor mass. Short-term fasting or treatment with several chemically unrelated autophagy-inducing CRMs, including hydroxycitrate and spermidine, improved the inhibition of tumor growth by chemotherapy in vivo. This effect was only observed for autophagy-competent tumors, depended on the presence of T lymphocytes, and was accompanied by the depletion of regulatory T cells from the tumor bed. [ABSTRACT FROM AUTHOR]

Abstract: Cell entry of severe acute respiratory syndrome coronavirus (SARS-CoV) is mediated by the viral spike (S) protein. Amino acids 319–510 on the S protein have been mapped as the receptor-binding domain (RBD), which mediates binding to the SARS-CoV receptor angiotensin converting enzyme 2 (ACE2) on SARS-CoV susceptible cells. In this study, we expressed a fusion protein containing the human codon-optimized RBD of the SARS-CoV spike protein linked to the Fc portion of human IgG1 (named RBD-Fc) in HEK293 cells. The RBD-Fc protein was purified by affinity chromatography. The flow cytometry assay showed that the purified RBD-Fc protein could bind to ACE2. We demonstrated that the RBD spike protein alone could be internalized into SARS-CoV susceptible cells together with ACE2. We also showed that the removal of N-glycans from the RBD spike protein did not abolish this phenomenon. Our discoveries may have some implications for the development of the SARS vaccine. [Copyright &y& Elsevier]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

Background: Since FTO was recognized as the first m6A demethylase, the understanding of its biological function has been widely expanded. However, the role of FTO in cervical cancer tumorigenesis remains unclear. Methods: In this study, we first analyzed the expression of FTO in two independent human cancer datasets and evaluated the correlation between FTO level and cervical cancer progression. Using small hairpin RNA technology, we explored the function of FTO in cervical cancer cell line Hela and SiHa cells, respectively. We then determined the FTO targets by performing transcriptional profile with FTO deficient and competent Hela cells, and finally validated these targets with ribosome profiling and functional rescue experiments. Results: Our data suggested that FTO was frequently overexpressed in human cervical cancer tissues and highly correlated with cervical cancer progression. FTO serves as an oncogenic regulator for cervical cancer cells' proliferation and migration which is vastly depended on its demethylase activity. Mechanistically, FTO interacts with transcripts of E2F1 and Myc, inhibition of FTO significantly impairs the translation efficiency of E2F1 and Myc, however, either overexpress E2F1 or Myc sufficiently compensates the FTO deficiency which decreases cell proliferation and migration. Conclusions: Our study indicates that FTO plays important oncogenic role in regulating cervical cancer cells' proliferation and migration via controlling m6A modification of E2F1 and Myc transcripts. FTO represents a potential drug candidate for cervical cancer therapy. [ABSTRACT FROM AUTHOR]