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Background: Depletion of certain ribosomal proteins induces p53 activation, which is mediated mainly by ribosomal protein L5 (RPL5) and/or ribosomal protein L11 (RPL11). Therefore, RPL5 and RPL11 may link RPs and p53 activation. Thus, this study aimed to explore whether RPs interact with RPL11 and regulate p53 activation in lung adenocarcinoma (LUAD) cells., Methods: The endogenous RPL11-binding proteins in A549 cells were pulled down through immunoprecipitation and identified with a proteomics approach. Docking analysis and GST-fusion protein assays were used to analyze the interaction of ribosomal protein S27a (RPS27a) and RPL11. Co-immunoprecipitation and in vitro ubiquitination assays were used to detect the effects of knockdown of RPS27a on the interaction between RPS27a and RPL11, and on p53 accumulation. Cell cycle, apoptosis, cell invasion and migration, cell viability and colony-formation assays were performed in the presence of knockdown of RPS27a. The RPS27a mRNA expression in LUAD was analyzed on the basis of the TCGA dataset, and RPS27a expression was detected through immunohistochemistry in LUAD samples. Finally, RPS27a and p53 expression was analyzed through immunohistochemistry in A549 cell xenografts with knockdown of RPS27a., Results: RPS27a was identified as a novel RPL11 binding protein. GST pull-down assays revealed that RPS27a directly bound RPL11. Knockdown of RPS27a weakened the interaction between RPS27a and RPL11, but enhanced the binding of RPL11 and murine double minute 2 (MDM2), thereby inhibiting the ubiquitination and degradation of p53 by MDM2. Knockdown of RPS27a stabilized p53 in an RPL11-dependent manner and induced cell viability inhibition, cell cycle arrest and apoptosis in a p53-dependent manner in A549 cells. The expression of RPS27a was upregulated in LUAD and correlated with LUAD progression and poorer prognosis. Overexpression of RPS27a correlated with upregulation of p53, MDM2 and RPL11 in LUAD clinical specimens. Knockdown of RPS27a increased p53 activation, thus, suppressing the formation of A549 cell xenografts in nude mice., Conclusions: RPS27a interacts with RPL11, and RPS27a knockdown enhanced the binding of RPL11 and MDM2, thereby inhibiting MDM2-mediated p53 ubiquitination and degradation; in addition, RPS27a as important roles in LUAD progression and prognosis, and may be a therapeutic target for patients with LUAD., (© 2022. The Author(s).)

Objective: Carbon ions suppress the effect of glutathione peroxidase 4 (GPX4) on the proliferation and metastasis of lung adenocarcinoma A549 cells. Methods: The clonogenic formation ability of A549 cells was calculated with different ray doses of radiation. Cell proliferation, cycle, and apoptosis of A549 cells after different ray irradiation were detected by cck8 and flow cytometry. The transwell assay was used to detect the cell migration and invasion after different rays of radiation to A549 cells. The GPX4 matrix metalloproteinase 2 and E‐cadherin expression levels were assessed by immunofluorescence and western blot. Results: At the dose of 4 Gy, A549 cell viability was 22.95 ± 5.00% and 55.52 ± 3.26% when treated with carbon ions and X‐rays, respectively. The distribution of A549 cells arrested in the G2 phase by carbon ion irradiation was positively correlated with radiation dose, with a most significant increase at 4 Gy irradiation (t = 4.303, p < 0.05). The results of apoptosis after irradiation showed were no significant differences in apoptosis at 1 and 2 Gy of X‐ray compared with 0 Gy, and 4 Gy irradiation significantly induced apoptosis in A549 cells (t = 30.520, p < 0.05). The apoptotic rate of carbon ion‐irradiated cells increased in a dose‐dependent manner and was the highest at 4 Gy (t = 17.356, p < 0.05). The transwell assays showed significantly decreased migration and invasion of both ray‐irradiated cells compared with the 0 Gy control cells. The carbon ions of 2 and 4 Gy significantly inhibited A549 cell migration (t2Gy = 9.260, t4Gy = 19.052, both p < 0.05) and invasion compared with those in the control cells (t2Gy = 6.141, t4Gy = 12.700, both p < 0.05). Treatment with 2 and/or 4 Gy doses of carbon ion reduced GPX4 (t2Gy = 8.170, t4Gy = 13.811, both p < 0.05) and matrix metalloproteinase 2 (t2Gy = 207.620, t4Gy = 93.170, both p < 0.05) protein expression, but E‐cadherin expression was increased (t2Gy = 62.811, t4Gy = 102.106, both p < 0.05). Conclusion: Compared with X‐ray irradiation, carbon ions have a higher relative biological effectiveness and can increase the proportion of A549 cells arrested in the G2/M stage to induce apoptosis, thereby inhibiting proliferation. At the same dose with X‐ray, carbon ions may inhibit the migration and invasion of A549 cells by regulating the expression of GPX4, matrix metalloproteinase 2, and E‐cadherin. [ABSTRACT FROM AUTHOR]