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BACKGROUND: Unfolded protein response (UPR)-mediated tumor-promoting functions have been identified in multiple cancers, and this study focused on investigating the role and molecular mechanisms of UPR in modulating gastric cancer (GC) pathogenesis. METHODS: The bioinformatics analysis was performed to examine the expression status of cancer associated genes in patients with stomach adenocarcinoma (STAD) and predict the targeting sites of miR-224-5p with LncRNA MIR503HG and TUSC3. Genes expressions were quantified by Real-Time qPCR, Western Blot and immunohistochemistry (IHC). Cell proliferation, viability, apoptosis and mobility were evaluated by MTT assay, trypan blue staining assay, flow cytometer and transwell assay, respectively. The binding sites were validated by dual-luciferase reporter gene system assay. RESULTS: LncRNA MIR503HG and TUSC3 were downregulated, but miR-224-5p was upregulated in GC tissues and cells, in contrast with their normal counterparts. Further gain- and loss-of-function experiments validated that the malignant phenotypes in GC cells, including cell proliferation, invasion, epithelial-mesenchymal transition (EMT) and tumorigenesis, were negatively regulated by LncRNA MIR503HG. Mechanistically, LncRNA MIR503HG upregulated TUSC3 in GC cells through sponging miR-224-5p, resulting in the repression of GC progression. Finally, we validated that knock-down of ATF6, but not other two branches of UPR (PERK1 and IRE1), partially rescued cell proliferation and EMT in the GC cells with LncRNA MIR503HG overexpression. CONCLUSIONS: Targeting the LncRNA MIR503HG/miR-224-5p/TUSC3 signaling cascade suppressed ATF6-mediated UPR, resulting in the blockage of GC development.
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BACKGROUND: Since 1923, only a few hundred cases of pulmonary arterial sarcoma (PAS) have been reported. It is easy for PAS to be misdiagnosed as pulmonary thromboembolism, which makes treatment difficult. The median survival time without surgical treatment for PAS is only 1.5-3 mo. Echocardiography is widely used in screening for pulmonary artery space-occupying lesions in patients with chest pain, dyspnea, and cough; furthermore, it is typically considered the first imaging examination for patients with PAS. CASE SUMMARY: In May 2017, a 39-year-old male patient experienced chest pain with no particular obvious cause. At that time, the cause was thought to be pulmonary embolism. In July 2017, positron emission tomography-computed tomography revealed space-occupying lesions in the right lung and multiple metastases in both lungs. The lesions of the right lung were biopsied, and pathology revealed undifferentiated sarcoma. Chemotherapy had been performed since July 2017 in another hospital. In December 2019, the patient was admitted to our hospital for the sake of CyberKnife treatment. Echocardiography suggested: (1) A right ventricular outflow tract (RVOT) solid mass of the main pulmonary artery; and (2) mild pulmonary valve regurgitation. Ultrasonography showed the absence of a thrombus in the deep veins of either lower limb. CONCLUSION: PAS is a single, central space-occupying lesion involving the RVOT and pulmonary valve. Echocardiography of PAS has its own characteristics.
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Colorectal cancer (CRC) is a gastrointestinal malignancy originating from either the colon or the rectum. A growing number of researches prove that the unfolded protein response (UPR) is closely related to the occurrence and progression of colorectal cancer. The UPR has three canonical endoplasmic reticulum (ER) transmembrane protein sensors: inositol requiring kinase 1 (IRE1), pancreatic ER eIF2α kinase (PERK), and activating transcription factor 6 (ATF6). Each of the three pathways is closely associated with CRC development. The three pathways are relatively independent as well as interrelated. Under ER stress, the activated UPR boosts the protein folding capacity to maximize cell adaptation and survival, whereas sustained or excessive ER triggers cell apoptosis conversely. The UPR involves different stages of CRC pathogenesis, promotes or hinders the progression of CRC, and will pave the way for novel therapeutic and diagnostic approaches. Meanwhile, the correlation between different signal branches in UPR and the switch between the adaptation and apoptosis pathways still need to be further investigated in the future.