Background:The study aimed to explore the clinical value of mitochondrial ribosomal protein L18(MRPL18)in breast cancer.Methods:Multiple databases were used to validate the expression of MRPL18.The prognostic impact a...Background:The study aimed to explore the clinical value of mitochondrial ribosomal protein L18(MRPL18)in breast cancer.Methods:Multiple databases were used to validate the expression of MRPL18.The prognostic impact and predictive value of MRPL18 were evaluated by using predictive models.Protein-protein interaction(PPI)networks were constructed by using GeneMANIA.Enrichment analysis is used to explore the signaling pathway regulated by MRPL18.Cell counting kit-8(CCK-8)assays,colony formation,migration assays,flow cytometry,and xenograft models were employed to evaluate the role of MRPL18 in tumor progression.The immune response of MRPL18 was examined using correlation analysis.Results:High levels of MRPL18 are considered a risk factor in breast cancer.In vitro and in vivo studies demonstrated that MRPL18 promotes proliferation and migration in breast cancer.Besides,results found that MRPL18 promotes tumor growth through the activation of phosphatidylinositol 3-kinase(PI3K).Furthermore,high MRPL18 expression was linked to reduced immunotherapy efficacy,as indicated by correlations with immune checkpoints and immune-infiltrating patterns.Conclusion:MRPL18 promotes the progression of breast cancer.展开更多
BACKGROUND Gastric carcinoma(GC)is a digestive system disease with high morbidity and mortality.However,early clinical detection is difficult,and the therapeutic effect for advanced disease is not satisfactory.Thus,fi...BACKGROUND Gastric carcinoma(GC)is a digestive system disease with high morbidity and mortality.However,early clinical detection is difficult,and the therapeutic effect for advanced disease is not satisfactory.Thus,finding new tumor markers and therapeutic targets conducive to the treatment of GC is imperative.MRPL35 is a member of the large subunit family of mitochondrial ribosomal protein.MRPL35 shows the characteristic of oncogene in colorectal cancer and esophageal cancer,which promotes the exploration of the correlation between MRPL35 and GC.We proposed that the expression of MRPL35 might be critical in GC.AIM To study the effect of MRPL35 knockdown on GC cell proliferation.METHODS The expression of MRPL35 in GC was evaluated based on data from the publictumor database UALCAN(www.ualcan.path.uab.edu).The effect of theexpression of MRPL35 on the prognosis was evaluated with KMplot(www.kmplot.com).The expression of MRPL35 was assessed on the tissuemicroarray by immunohistochemistry and the level of MRPL35 mRNA in 25 pairsof clinical GC tissues and matched adjacent tissues was detected by quantitativereverse transcription-polymerase chain reaction.Celigo cell count assay,colonyformation assay,and flow cytometry were used to assess the role of MRPL35 inGC cell proliferation and apoptosis in vitro.Additionally,tumor formationexperiment in BALB/c nude mice was utilized to determine the effect of MRPL35on GC cell proliferation.After knockdown of MRPL35,related proteins wereidentified by isobaric tags for relative and absolute quantification analysis,andthe expression of related proteins was detected by Western blot.RESULTSThe expression of MRPL35 was up-regulated in GC(P=1.77×10^(-4)).The Kaplan-Meier plots of the overall survival indicated that high expression of MRPL35 wasassociated with a poor survival in GC.Compared with adjacent tissues,theexpression of MRPL35 in GC tissues was increased,which was related to age(P=0.03),lymph node metastasis(P=0.007),and pathological tumor-node-metastasisstage(P=0.024).Knockdown of MRPL35 inhibited GC cell proliferation andcolony formation and induced apoptosis.Animal experiment results showed thatknockdown of MRPL35 inhibited tumor formation in BALB/c nude mice.Westernblotting analysis showed that after knockdown of MRPL35,the expression ofPICK1 and BCL-XL proteins decreased,and that of AGR2 protein increased.CONCLUSIONCollectively,our findings demonstrate that knockdown of MRPL35 inhibits GCcell proliferation through related proteins including PICK1,BCL-XL,and AGR2.展开更多
基金supported by grants from the Key Project of Scientific Research Plan of Hunan Provincial Health Commission(C202301047982,Wei Du)Changde City Science and Technology Innovation Guidance Plan Project(2022ZD39,Wei Du)+1 种基金the Wings Scientific and Technological Foundation of The First People’s Hospital of Changde City(2022ZZ05,Wei Du,2024ZC02,Rong Xu,Z2025ZC04,Hailong Li)The Science and Technology Innovation Program of Changde City(2024ZD248,Rong Xu,2024ZD200,Yun Peng).
文摘Background:The study aimed to explore the clinical value of mitochondrial ribosomal protein L18(MRPL18)in breast cancer.Methods:Multiple databases were used to validate the expression of MRPL18.The prognostic impact and predictive value of MRPL18 were evaluated by using predictive models.Protein-protein interaction(PPI)networks were constructed by using GeneMANIA.Enrichment analysis is used to explore the signaling pathway regulated by MRPL18.Cell counting kit-8(CCK-8)assays,colony formation,migration assays,flow cytometry,and xenograft models were employed to evaluate the role of MRPL18 in tumor progression.The immune response of MRPL18 was examined using correlation analysis.Results:High levels of MRPL18 are considered a risk factor in breast cancer.In vitro and in vivo studies demonstrated that MRPL18 promotes proliferation and migration in breast cancer.Besides,results found that MRPL18 promotes tumor growth through the activation of phosphatidylinositol 3-kinase(PI3K).Furthermore,high MRPL18 expression was linked to reduced immunotherapy efficacy,as indicated by correlations with immune checkpoints and immune-infiltrating patterns.Conclusion:MRPL18 promotes the progression of breast cancer.
文摘BACKGROUND Gastric carcinoma(GC)is a digestive system disease with high morbidity and mortality.However,early clinical detection is difficult,and the therapeutic effect for advanced disease is not satisfactory.Thus,finding new tumor markers and therapeutic targets conducive to the treatment of GC is imperative.MRPL35 is a member of the large subunit family of mitochondrial ribosomal protein.MRPL35 shows the characteristic of oncogene in colorectal cancer and esophageal cancer,which promotes the exploration of the correlation between MRPL35 and GC.We proposed that the expression of MRPL35 might be critical in GC.AIM To study the effect of MRPL35 knockdown on GC cell proliferation.METHODS The expression of MRPL35 in GC was evaluated based on data from the publictumor database UALCAN(www.ualcan.path.uab.edu).The effect of theexpression of MRPL35 on the prognosis was evaluated with KMplot(www.kmplot.com).The expression of MRPL35 was assessed on the tissuemicroarray by immunohistochemistry and the level of MRPL35 mRNA in 25 pairsof clinical GC tissues and matched adjacent tissues was detected by quantitativereverse transcription-polymerase chain reaction.Celigo cell count assay,colonyformation assay,and flow cytometry were used to assess the role of MRPL35 inGC cell proliferation and apoptosis in vitro.Additionally,tumor formationexperiment in BALB/c nude mice was utilized to determine the effect of MRPL35on GC cell proliferation.After knockdown of MRPL35,related proteins wereidentified by isobaric tags for relative and absolute quantification analysis,andthe expression of related proteins was detected by Western blot.RESULTSThe expression of MRPL35 was up-regulated in GC(P=1.77×10^(-4)).The Kaplan-Meier plots of the overall survival indicated that high expression of MRPL35 wasassociated with a poor survival in GC.Compared with adjacent tissues,theexpression of MRPL35 in GC tissues was increased,which was related to age(P=0.03),lymph node metastasis(P=0.007),and pathological tumor-node-metastasisstage(P=0.024).Knockdown of MRPL35 inhibited GC cell proliferation andcolony formation and induced apoptosis.Animal experiment results showed thatknockdown of MRPL35 inhibited tumor formation in BALB/c nude mice.Westernblotting analysis showed that after knockdown of MRPL35,the expression ofPICK1 and BCL-XL proteins decreased,and that of AGR2 protein increased.CONCLUSIONCollectively,our findings demonstrate that knockdown of MRPL35 inhibits GCcell proliferation through related proteins including PICK1,BCL-XL,and AGR2.
