Up to 10–20% of patients with coronavirus disease 2019 (COVID‐19) develop a severe pulmonary disease due to immune dysfunction and cytokine dysregulation. However, the extracellular proteomic characteristics in respiratory tract of these critical COVID‐19 patients still remain to be investigated. In the present study, we performed a quantitative proteomic analysis of the bronchoalveolar lavage fluid (BALF) from patients with critical COVID‐19 and from non‐COVID‐19 controls. Our study identified 358 differentially expressed BALF proteins (P < 0.05), among which 41 were significantly changed after using the Benjamini–Hochberg correction (q < 0.05). The up‐regulated signaling was found to be mainly involved in inflammatory signaling and response to oxidative stress. A series of increased extracellular factors including Tenascin‐C (TNC), Mucin‐1 (KL‐6 or MUC1), Lipocalin‐2 (LCN2), periostin (POSTN), Chitinase 3‐like 1 (CHI3L1 or YKL40), and S100A12, and the antigens including lymphocyte antigen 6D/E48 antigen (LY6D), CD9 antigen, CD177 antigen, and prostate stem cell antigen (PSCA) were identified, among which the proinflammatory factors TNC and KL‐6 were further validated in serum of another thirty‐nine COVID‐19 patients and healthy controls, showing high potentials of being biomarkers or therapeutic candidates for COVID‐19. This BALF proteome associated with COVID‐19 would also be a valuable resource for researches on anti‐inflammatory medication and understanding the molecular mechanisms of host response. Database Proteomic raw data are available in ProteomeXchange (http://proteomecentral.proteomexchange.org) under the accession number PXD022085, and in iProX (http://www.iprox.org) under the accession number IPX0002429000.

Hepatocellular carcinoma (HCC) is a worldwide malignance and displays marked vascular abnormalities and active metastasis. MicroRNAs (miRNAs) have been shown to play important roles in regulating tumor properties in cancer, however, whether miR-497 contributes to HCC angiogenesis or metastasis remains unclear. In this study, we found that miR-497 was significantly down-regulated in HCC tissue samples and cell lines. Gain-of-function and loss-of-function studies revealed that miR-497 could repress both the pro-angiogenic and metastatic ability of HCC cells. Subsequent investigations disclosed that miR-497 directly inhibited the 3′-untranslated regions (UTRs) of vascular endothelial growth factor A (VEGFA) and astrocyte elevated gene-1 (AEG-1). Furthermore, overexpression of these targets antagonized the function of miR-497. Based on nude mouse models, we demonstrated that overexpression of miR-497 significantly repressed microvessel densities in xenograft tumors and reduced pulmonary metastasis. In conclusion, our findings indicate that miR-497 downregulation contributes to angiogenesis and metastasis in HCC.

Growing tumor cells possess a distinct metabolic phenomenon that allows them to preferentially utilize glucose through aerobic glycolysis, which is referred to as the “Warburg effect.” Accumulating evidence suggests that microRNAs (miRNAs) could regulate such metabolic reprogramming. Our microarray analysis and quantitative real-time PCR validation revealed that miR-885-5p was strongly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. To investigate miR-885-5p’s biological functions in HCC progression, malignant phenotypes were analyzed in different types of hypoxic model and indicated that overexpression of miR-885-5p significantly inhibited HCC cell proliferation and migration and induced apoptosis in vitro and tumor growth in vivo. Subsequent investigations of whether miR-885-5p regulated the glycometabolic activity of cancer cells demonstrated that forced expression of miR-885-5p in SMMC-7721 cells significantly reduced glucose uptake and lactate production by repressing several key enzymes related to glycolysis. Particularly, miR-885-5p directly targets the 3′ UTR of hexokinase 2 (HK2), which is a key enzyme that catalyzes the irreversible first step of glycolysis and associates with poor patient outcomes. The miR-885-5p/HK2 axis strongly links aerobic glycolysis to carcinogenesis and may become a promising therapeutic target and prognostic predictor for HCC patients.