XBP1s promotes the development of lung adenocarcinoma via the p‑JNK MAPK pathway

Abstract

Spliced X-box binding protein 1 (XBP1s) has been reported to participate in the pathogenesis of numerous types of cancer; however, whether XBP1s plays a role in lung cancer remains to be elucidated. In the present study, bioinformatics analysis was performed to determine the mRNA expression level of XBP1 in lung cancer and adjacent normal tissues. Gene Ontology terms, pathway enrichment and Pearson's correlation analysis were performed to investigate the possible mechanism involved. Western blot and reverse transcription-quantitative PCR were performed to quantify the protein and mRNA expression level of target proteins, respectively. Small interfering RNA or overexpression plasmid were used to knockdown or overexpress the expression level of XBP1s. EdU staining, colony formation, Cell Counting Kit-8, Transwell and wound healing assays, and flow cytometry were performed to detect the proliferation, colony forming ability, cell viability, migration and invasion ability, and the apoptosis rate. The results showed that the mRNA and protein expression level of XBP1 was higher in tumor tissues compared with that in adjacent normal tissues using data from the TIMER2.0, ONCOMINE and UALCAN online databases. In addition, the mRNA expression level of XBP1 was also associated with clinical features, including age, smoking habit, individual cancer stage and nodal metastasis status. In the in vitro experiments, the mRNA and protein expression level of XBP1s was increased in the A549 cell line compared with that in the human bronchial epithelial (HBE), H1299, PC9 and H460 cell lines. Hypoxia further increased the protein expression level of XBP1s in the A549 cell line. Knockdown of XBP1s expression in the A549 cell line resulted in decreased proliferation, colony formation, cell viability, migration and invasion, and increased apoptosis. By contrast, overexpressing XBP1s in the HBE cell line led to the opposite results. To investigate the mechanism involved, proteins associated with XBP1 were analyzed using the LinkedOmics database. Pathway enrichment revealed the MAPK pathway to be the possible XBP1 downstream target. Furthermore, Pearson's correlation and western blot analyses verified that phosphorylated (p)-JNK rather than p-ERK or p-p38 was the downstream effector of XBP1s. Phosphorylation of JNK was decreased when XBP1s expression was knocked down in the A549 cell line under normoxic and hypoxic conditions. Inhibiting p-JNK with SP600125 reversed the increased prosurvival effects caused by XBP1s overexpression. The results from the present study suggest that XBP1s/p-JNK function as a prosurvival factors in the A549 cell line and could be a potential target for the treatment of lung adenocarcinoma.

Nickel alginate‐enhanced fire safety of aluminum diethylphosphinate on epoxy resin

“…As shown in Figure 2b, FR‐EPs exhibit two thermal oxidative degradation processes, showing the similar decomposition behaviors with EP. The addition of phosphorus‐containing FRs usually causes the decrease of thermal stability 38,39 . However, the incorporation of AlPi and nickel alginate do not change the T 5% , T max1 , R max1 , T max2 , and R max2 of EP, which can be attributed to the lower content (4%) of AlPi and nickel alginate.…”

“…The addition of phosphorus-containing FRs usually causes the decrease of thermal stability. 38,39 However, the incorporation of AlPi and nickel alginate do not change the T 5% , T max1 , R max1 , T max2 , and R max2 of EP, which can be attributed to the lower content (4%) of AlPi and nickel alginate. And the char residues at 700 C of FR-EPs are achieved to 2.5% (EP/AlPi), 2.9% (EP/AlPi 9.5 -Nickel Alginate 0.5 ) and 2.7% (EP/AlPi 9.0 -Nickel Alginate 1.0 ), which are obviously higher than that of EP (0.4%).…”

Unveiling the role of RAC3 in the growth and invasion of cisplatin‐resistant bladder cancer cells

“…Numerous studies have shown that the JNK/MAPK pathway significantly affects the development of cancer cells in various tumours. Specific p‐JNK inhibition can considerably reduce the proliferation and migration of cancer cells such as lung adenocarcinoma, oesophageal squamous cell carcinoma, and colon cancer cells, and can greatly induce the apoptosis of some cancer cells 38–41 . By influencing the expression of many molecules, the JNK signalling pathway can increase the growth and metastasis of cancer cells, whereas JNK activation can also inhibit apoptosis by inducing autophagy in various cancers.…”

“…[8][9][10]33 can greatly induce the apoptosis of some cancer cells. [38][39][40][41] By influencing the expression of many molecules, the JNK signalling pathway can increase the growth and metastasis of cancer cells, whereas JNK activation can also inhibit apoptosis by inducing autophagy in various cancers. In cancer treatment, the activation of JNK pathway can promote the expression of PD-L1, thereby enhancing the immune escape of tumours.…”