The Role Of MRPL35 Protein In The Tumorigenesis And Development In Colorectal Cancer

Background & Aims:Mitrochondrial ribosomal proteins(MRPs)are the major components of mitochondrial ribosome,which are involved in mitochondrial translation system.These proteins are synthesized in the cytoplasm and imported into the mitochondrion where they are assembled into the ribosome.Interestingly,a variety of MRPs have been found abnormally expressed in and associated with the development of malignant tumours.Our previous works identified that human mitochondrial ribosomal protein L35(MRPL35)was up-regulated in a couple of colorectal cancer cells.The present study was designed to explore the role of MRPL35 in tumorigenesis and development of colorectal cancer.Methods:The tissue microarray was generated from formalin-fixed,paraffin-embeded tissues of151 patients with CRC.The MRPL35 m RNA and protein levels were also measured in paired tumor and nontumor colon tissues collected from 26 patients.The effect of MRPL35 expression on patient survival was evaluated by the Kaplan-Meier survival curve.Risk ratios of patient survival associate with MRPL35 expression and other variables were estimated by univariate and multivariate Cox regression model.Expression of MRPL35 was knocked down in CRC cell lines(HCT116 and SW480);cells were analyzed for colony formation,proliferation and apoptosis.Results:The levels of MRPL35 mRNA and protein were increased in colorectal tumor tissues,compared with matched nontumor colon tissues(P<0.05);protein levels was positive correlated with lymphode metastasis,distant metastasis and TNM stages(P<0.05);increased protein levels were associated with shorter survival times of patients(P<0.05).Knockdown of MRPL35 in HCT116 and SW480 cells reduced their proliferation about 85 % and 71 %,leading to apoptosis(increased 72%and 100%)and cell cycle arrest at G2/M phase compared to cells without MRPL35 knockdown.Conclusion:MRPL35 promotes proliferation of CRC cells.Patients with colorectal tumors that express increased levels of MRPL35 have shorter survival times than patients whose tumors have lower levels.The molecular mechanism of MRPL35 needs to be further investigated.