ABSTRACT
Osteosarcoma (OS) has strong invasiveness, early metastasis, high drug resistance, and poor prognosis. At present, OS still lacks reliable biomarkers, which makes early diagnosis of OS more difficult. AOC3 is highly expressed in OS and highly correlated with lung metastasis. qRT-PCR could identify mRNA levels of genes. Immunohistochemistry and Western blot assays could detect protein levels. Immunofluorescence and ELISA assays were applied to evaluate the activation of neutrophils. Additionally, transwell and wound healing assays evaluated cell migration and invasion abilities. Tube formation and sphere-forming assays were applied to detect the angiogenesis. C57BL/6 mice were injected with OS cells to establish a xenograft tumor model to observe the lung metastasis of OS. Flow cytometry is used to evaluate the ability of tumor cells to recruit neutrophils. AOC3 was significantly overexpressed in OS, and down-regulation of AOC3 could inhibit OS migration, invasion, and angiogenesis. AOC3 could increase tumor development and lung metastasis of OS in vivo experiments. The promoting effect of AOC3 on tumor lung metastasis was achieved by recruiting tumor neutrophils. Activated NETs could up-regulate the metastatic ability of OS cells. Tumor neovascularization also played a role in metastasis, and AOC3 supported tumor neovascularization. AOC3 accelerates lung metastasis of OS by recruiting tumor-related neutrophils and utilizing NETs and tumor vascularization formation.
ABSTRACT
In eukaryotic cells, primases are the key polymerase during DNA replication and DNA damage repair, which includes primase subunit 1 (PRIM1) and primase subunit 2 (PRIM2). Recent studies reported that the aberrant expression and activity of PRIM enzymes are closely associated with the carcinogenesis and development of various cancers. PRIM1 is overexpressed in hepatocellular carcinoma, breast cancer, and other cancers, while PRIM2 is highly expressed in lung cancer, gastrointestinal cancer, and other cancers. Further studies revealed that the knockdown of PRIM1 promoted the apoptosis of liver cancer cells, while Dihydroartemisinin (DHA) can inhibit PRIM2 expression, suppress lung cancer cell proliferation, and result in ferroptosis. The present review summarized the recent advancements in the research of the aberrant expression of PRIM1 and PRIM2 and their activity in DNA replication, DNA damage repair, and carcinogenesis. Furthermore, the strategies targeting PRIM1 or/and PRIM2 become potential therapeutic approaches in cancer treatment.
ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic has imposed enormous morbidity and mortality burdens. Patients with rheumatic diseases (RDs) are vulnerable to the COVID-19 infection, given their immunocompromised status. Ensuring acceptance of the COVID-19 vaccine is important and has attracted attention by health professionals. In this study, we designed an online cross-sectional survey that used an online questionnaire from 8 May 2021 to 4 October 2021. Attitudes toward the COVID-19 vaccination, personal information, current disease activity status, adverse events (AEs), and knowledge sources of vaccines were collected. Descriptive statistics, nonparametric tests, and ordinal logistic regression were used to analyze the data. A total of 1022 questionnaires were received, among which 70.2% (720/1022) of patients with RDs agreed to vaccination, while only 31.6% of patients were actually vaccinated. Male, employed, high-income patients and those with inactive disease showed a more positive attitude. Concerns of AEs and disease flare were the main factors affecting vaccination willingness. Only 29.6% (304/1022) of patients thought they had received enough information about the COVID-19 vaccine from their doctors. In conclusion, most patients with RDs in China intended to get vaccinated, although the vaccination rate in this particular population was low. Rheumatologists should take more responsibility in COVID-19 vaccination education of patients with RDs.