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Background: The aim of this study was to determine whether progesterone could inhibit the growth of lung adenocarcinoma cells via membrane progesterone receptor alpha (mPRα) and elucidate its potential mechanism. The relationship between mPRα expression and the survival prognosis of lung adenocarcinoma patients was studied. Methods: A mPRα knockdown lung adenocarcinoma cell line was constructed and treated with P4 and Org (a derivative of P4 and specific agonist of mPRα). Cell proliferation was assessed using CCK‐8 and plate colony formation assays. Protein expression was detected by western blotting. A nude mouse model of lung adenocarcinoma was established to assess the antitumor effect of P4/Org in vivo. Results: We initially determined that mPRα could promote the development of lung adenocarcinoma through the following lines of evidence. High expression of mPRα both at the mRNA and protein level was significantly associated with the poor prognosis of lung adenocarcinoma patients. The downregulation of mPRα inhibited the proliferation of lung adenocarcinoma cells. We further showed that mPRα mediates the ability of P4 to inhibit the growth of lung adenocarcinoma cells through the following lines of evidence: P4/Org inhibited the proliferation of lung adenocarcinoma cells; mPRα mediated the ability of P4/Org to inhibit lung adenocarcinoma cell proliferation; mPRα mediated the ability of P4/Org to inhibit the PKA (cAMP‐dependent protein kinase)/CREB (cAMP responsive element binding protein) and PKA/β‐catenin signaling pathways; and P4/Org inhibited the growth of a lung adenocarcinoma tumor model in vivo. Conclusions: In summary, the results of our study show that progesterone can inhibit lung adenocarcinoma cell growth via mPRα. [ABSTRACT FROM AUTHOR]

Simple Summary: Hypopharyngeal squamous cell carcinoma (HSCC) is a type of cancer with poor prognosis in head and neck tumors. More studies have shown that abnormal expression of lncRNA plays a crucial role in HSCC. Through RIP experiments, we confirmed that NR120519 interacts with KRT17, and the expression of both is closely related to the overall survival of HSCC. Subsequent experiments showed that both NR120519 and KRT17 could regulate the AKT/mTOR pathway and lead to EMT transformation, promoting the progression of HSCC. Therefore, NR120519/KRT17/AKT/mTOR axis has been identified as a new pathway, providing a feasible preliminary basis for future studies. Background: Hypopharyngeal carcinoma is the worst type of head and neck squamous cell carcinoma. It is necessary to identify the key molecular targets related to the carcinogenesis and development of hypopharyngeal carcinoma. Methods: Differentially expressed lncRNAs in hypopharyngeal carcinoma were selected by microarray, and lncRNA-associated proteins were found by RIP assay. Colony formation, CCK-8, wound healing and Transwell assays were performed to detect the effects of lncRNA and its associated protein on cell proliferation and migration in vitro. Downstream pathways of lncRNA and its associated protein were detected by WB. Through a subcutaneous tumor model, the effects of lncRNA and its associated protein on cell proliferation were detected. The expressions of lncRNA and its associated protein in hypopharyngeal cancer tissues were detected by qRT-PCR and immunohistochemistry assays, respectively, and survival analyses were performed by Kaplan-Meier curve. Results: A total of 542 and 265 lncRNAs were upregulated and downregulated in microarrays, respectively. LncRNA NR120519 was upregulated and promoted cell proliferation and migration of hypopharyngeal carcinoma in vitro and cell proliferation in vivo. RIP and WB assays showed that KRT17 was associated with and blocked by NR120519.The silencing of KRT17 promoted cell proliferation and the migration of hypopharyngeal carcinoma in vitro and cell proliferation in vivo by activating the AKT/mTOR pathway and epithelial-mesenchymal transformation (EMT). Finally, the NR120519 high expression and KRT17 low expression groups showed shorter overall survival. Conclusion: NR120519 activated the AKT/mTOR pathway and EMT by blocking KRT17 to promote cell proliferation and the migration of hypopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Aim To investigate the mechanism of endoplasmic reticulum (ER) stress-induced apoptosis as well as the protective action of basic fibroblast growth factor ( bFGF) both in vivo and in vitro. Methods and Results ER stress-induced apoptosis was involved in the injuries of spinal cord injury (SCI) model rat. bFGF administration improved the recovery and increased the survival of neurons in spinal cord lesions in model rat. The protective effect of bFGF is related to the inhibition of CHOP, GRP78 and caspase-12, which are ER stress-induced apoptosis response proteins. bFGF administration also increased the survival of neurons and the expression of growth-associated protein 43 (GAP43), which is related to neural regeneration. The protective effect of bFGF is related to the activation of downstream signals, PI3K/Akt/GSK-3β and ERK1/2, especially in the ER stress cell model. Conclusions This is the first study to illustrate that the role of bFGF in SCI recovery is related to the inhibition of ER stress-induced cell death via the activation of downstream signals. Our work also suggested a new trend for bFGF drug development in central neural system injuries, which are involved in chronic ER stress-induced apoptosis. [ABSTRACT FROM AUTHOR]