Radiation-induced muscle fibrosis is a long-term side effect of radiotherapy that significantly affects the quality of life and even reduces the survival of cancer patients. We have demonstrated that radiation induces satellite cell (SC) activation at the molecular level; however, cellular evidence in a rat model of radiation-induced muscle fibrosis was lacking. In this study, we evaluated SC activation in vivo and investigated whether radiation affects the proliferation and differentiation potential of SCs in vitro. For in vivo studies, Sprague-Dawley rats were randomly divided into six groups (n = 6 per group): non-irradiated controls, 90 Gy/1 week-, 90 Gy/2 weeks-, 90 Gy/4 weeks-, 90 Gy/12 weeks- and 90 Gy/24 weeks-postirradiation groups. Rats received a single dose of radiation in the left groin area and rectus femoris tissues were collected in the indicated weeks. Fibrosis, apoptosis, and autophagy were evaluated by Masson's trichrome staining, TUNEL staining, and electron microscopy, respectively. SC activation and central nuclear muscle fibers were evaluated by immunofluorescence staining and hematoxylin and eosin staining. IL-1β concentrations in serum and irradiated muscle tissue samples were determined by ELISA. For in vitro studies, SCs were isolated from rats with radiation-induced muscle fibrosis and their proliferation and differentiation were evaluated by immunofluorescence staining. In vivo, fibrosis increased over time postirradiation. Apoptosis and autophagy levels, IL-1β concentrations in serum and irradiated skin tissues, and the numbers of SCs and central nuclear muscle fibers were increased in the irradiated groups when compared with the control group. In vitro, cultured SCs from irradiated muscle were positive for the proliferation marker Pax7, and differentiated SCs were positive for the myogenic differentiation marker MyHC. This study provided cellular evidence of SC activation and proliferation in rats with radiation-induced muscle fibrosis.
Background: Nuclear receptor binding SET domain protein-3 (NSD3) has been reported to be a crucial regulator of carcinogenesis as a histone lysine methyltransferase in multiple cancer types. However, the underlying mechanisms have not been clearly delineated. Therefore, we aimed to investigate the expression pattern, prognostic value, and potential function of NSD3 in 33 types of human cancer. Methods: The potential roles of NSD3 were explored using datasets from The Cancer Genome Atlas (TCGA) pan-cancer dataset and an array of bioinformatics methods, including analyses of the relationship between NSD3 expression and prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), DNA amplification, and immune cell infiltration across 33 cancer types. Results: Many types of cancers are characterized according to the dysregulation of NSD3, which is associated with the pathological stage of cancer. Patients in our study with higher NDS3 levels, which were attributed to NSD3 copy number amplification, always experienced shorter survival periods. Additionally, NSD3 expression was associated with TMB and MSI in 10 different cancer types. The top five cancers whose NSD3 expression correlated with immune scores were further analyzed. The levels of immune-cell infiltration differed significantly between high and low NSD3-expressing samples in each of the five cancer types. Functional enrichment of the NSD3 co-expressed genes indicated a role for NSD3 in the regulation of immune responses and tumorigenesis. Conclusions: Our study revealed that NSD3 can function as a prognostic marker in various cancers due to its role in tumorigenesis and tumor immunity.
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