Colorectal cancer (CRC) is the third main cause of cancer-relevant deaths worldwide, and its incidence has increased in recent decades. Previous studies have indicated that certain long non-coding RNAs (lncRNAs) have regulatory roles in tumor occurrence and progression. Often, lncRNAs are competitive endogenous RNAs (ceRNAs) which sponge miRNAs to up-regulate mRNAs. Here, we examined the role of a novel lncRNA BBOX1 antisense RNA 1 (BBOX1-AS1) in colorectal cancer (CRC). We observed that BBOX1-AS1 is overexpressed in CRC cell lines, and BBOX1-AS1 knockdown enhances cell proliferation, migration and invasion while reducing cell apoptosis. MiR-361-3p is present at a low level in CRC and is negatively modified by BBOX1-AS1. Moreover, miR-361-3p was validated to be targeted by BBOX1-AS1. SH2B1 was notably up-regulated in CRC cell lines, and identified as a downstream gene of miR-361-3p. In addition, we found that miR-361-3p amplification can suppress the expression of SH2B1. Finally, data from rescue assays suggested that overexpression of SH2B1 counteracted BBOX1-AS1 silencing-mediated inhibition of CRC progression. In conclusion, BBOX1-AS1 promotes CRC progression by sponging hsa-miR-361-3p and up-regulating SH2B1.
Background: This study ought to further explore the anti-tumor effects of Sophoridine on gastric cancer cells.Methods: Cell viability assay (CCK-8 assay) was used to measure the IC50 values of Sophoridine on gastirc cancer AGS and SGC7901 cell lines and normal gastric epithelial cell line GES-1. EdU and colony formation assay were performed to confirm the cytotoxic effect of Sophoridine on AGS and SGC7901 cells. The apoptotic effects of Sophoridine on AGS and SGC7901 cells were measured by Flow cytometry. Transwell assay was used to evaluate the effects of Sophoridine on migration and invasion of AGS and SGC7901 cells. The protein expression of Sophoridine on AGS and SGC7901 cells were detected via Western blot. Results: We demonstrated that Sophoridine exerts potent tumor-suppressive activities, including inhibition of proliferation, colony formulation, migration and invasion, as well as induction of apoptosis of gastric cancer cells. In addition, we further showed that Sophoridine induces G2/M cell cycle arrest via inhibiting double-stranded DNA breaks repair and enhances the efficacy of cisplatin in gastric cancer cells. Molecular studies further revealed that Sophoridine depends on Estrogen-related receptor gamma (ESRRG) to perform tumor-suppressive activities and which leads to the degradation of β-catenin in an ubiquitin-proteasome pathway independent manner.Conclusions: Our study provided the promising preclinical anti-tumor evidence for the potential application of Sophoridine against gastric cancer.
Purpose: For the emerging pandemic Coronavirus Disease 2019 (COVID-19), no clear description on its deaths’ clinical characteristics and causes of death is available. Hence, this study analyzed clinical characteristics of 77 COVID-19 deaths, providing data support to further understand this disease.Method: A retrospective analysis of 77 COVID-19 deaths in East Branch, Renmin Hospital of Wuhan University from February 1 to March 7, 2020 was performed in clinical characteristics, laboratory results, causes of death, and subgroup comparison. Results: Totally 72.7% of the deaths (male-female ratio: 51:26, average age at death: 71, mean survival time: 17.4 days) had hypertension, heart disease, diabetes, chronic lung disease, and other comorbidities. Acute respiratory distress syndrome (ARDS) and sepsis were the main causes of death. Increases in C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer and lactic acid (LAC), and decreases in lymphocyte, cluster of differentiation (CD) 4+ and CD8+ cells were common in laboratory results. Subgroup analysis showed: 1) Most female deaths had cough and diabetes. 2) The male proportion in young and middle-aged deaths was higher; while elderly deaths were more prone to myocardial injury and elevated CRP. 3) There was no statistical difference between short-term and non-short-term survival subgroups. 4) CRP and LDH increased and CD4+ and CD8+ cells decreased significantly in patients with hypertension.Conclusions: The majority of COVID-19 deaths are males, especially the elderly with underlying diseases. The main causes of death include ARDS and sepsis. Most female deaths have cough and diabetes. Myocardial injury is common in elderly deaths. Patients with hypertension are prone to increased inflammatory index, tissue hypoxia and cellular immune injury.Authors Kaige Wang and Zhixin Qiu contributed equally to this work.
Background p53 isoform Δ133p53 is directly transactivated by p53 and antagonizes p53 activities in cancer progression. However, its correlation with prognosis and cancer recurrence in esophageal squamous cell carcinoma (ESCC) is still unclear.Methods Expression of Δ133p53 and Δ133p53/full-length p53 (FLp53) in tissues and serums of 180 ESCC patients was evaluated using qRT-PCR.Results Tissue Δ133p53 expression and Δ133p53/FLp53 ratio were significantly increased in ESCC tissue compared with adjacent normal tissue. Pre-operative Δ133p53 expression and Δ133p53/FLp53 ratio in tissue or serum samples were positively associated with TNM stage and post-operative recurrence. Kaplan-Meier curve and multivariate cox regression analyses revealed that the tissue and serum Δ133p53/FLp53 ratio (cutoff value: 2.9160) were independent prognostic factors for overall survival (OS) and progression-free survival (PFS) in ESCC patients, and showed no statistical difference in receiver-operating characteristic (ROC) curve analysis, while serum Δ133p53 showed no significant prognostic value. More importantly, the serum Δ133p53/FLp53 ratio in ESCC patients was significantly decreased within 72 h post tumor resection and patients with a consistently high serum Δ133p53/FLp53 ratio (≥ 2.9160) had higher recurrence rates than those with consistently low ratio values. In addition, dynamic detection in each follow-up timepoint showed that serum Δ133p53/FLp53 ratios were higher than 2.9160 upon recurrence, and they even increased prior to radiologic progression.Conclusion The serum Δ133p53/FLp53 ratio can be a novel predictor for survival outcome and may serve as a real-time parameter for monitoring recurrence in ESCC patients after surgery.
Background p53 isoform Δ133p53 is directly transactivated by p53 and antagonizes p53 activities in cancer progression. However, its correlation with prognosis and cancer recurrence in esophageal squamous cell carcinoma (ESCC) is still unclear.Methods Expression of Δ133p53 and Δ133p53/full-length p53 (FLp53) in tissues and serums of 180 ESCC patients was evaluated using qRT-PCR.Results Tissue Δ133p53 expression and Δ133p53/FLp53 ratio were significantly increased in ESCC tissue compared with adjacent normal tissue. Pre-operative Δ133p53 expression and Δ133p53/FLp53 ratio in tissue or serum samples were positively associated with TNM stage and post-operative recurrence. Kaplan-Meier curve and multivariate cox regression analyses revealed that the tissue and serum Δ133p53/FLp53 ratio (cutoff value: 2.9160) were independent prognostic factors for overall survival (OS) and progression-free survival (PFS) in ESCC patients, and showed no statistical difference in receiver-operating characteristic (ROC) curve analysis, while serum Δ133p53 showed no significant prognostic value. More importantly, the serum Δ133p53/FLp53 ratio in ESCC patients was significantly decreased within 72 h post tumor resection and patients with a consistently high serum Δ133p53/FLp53 ratio (≥ 2.9160) had higher recurrence rates than those with consistently low ratio values. In addition, dynamic detection in each follow-up timepoint showed that serum Δ133p53/FLp53 ratios were higher than 2.9160 upon recurrence, and they even increased prior to radiologic progression.Conclusion the serum Δ133p53/FLp53 ratio can be a novel predictor for survival outcome and may serve as a real-time parameter for monitoring recurrence in ESCC patients after surgery.
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