MRPL13 Promotes Tumor Cell Proliferation, Migration and EMT Process in Breast Cancer Through the PI3K-AKT-mTOR Pathway

Abstract

Purpose Breast cancer (BC), with varying histopathology, biology and response to systemic treatment, is the second leading cause of cancer-related mortality. Previous studies have inferred that the expression of mitochondrial ribosomal proteins (MRPs) is possibly related to the occurrence/progression of BC. MRPL13 might be one of the potential MRP candidates that are involved in BC tumorigenesis, but its role in BC has rarely been reported. The purpose of the current study was to evaluate the prognostic significance of MRPL13, as well as to explore its potential biological functions in BC. Materials and Methods A series of bioinformatic and statistical methods were adopted to assess the MRPL13 expression profile, its relationship with clinicopathological characteristics, copy number variation (CNV), impact on clinical outcomes and relevant functions. All the results are analysed by 1097 BC patients collected from The Cancer Genome Atlas (TCGA) dataset and 52 clinical samples for immunohistochemistry (IHC) assay. Results The results demonstrated that the expression of MRPL13 in BC tissues was remarkably elevated than that in normal breast tissues. In addition, the Kaplan-Meier curves and Cox model indicated that patients with high MRPL13 expression were connected to a worse prognosis, heralding the independent prognostic value of this protein in BC. Moreover, an enrichment analysis showed that MRPL13 was mainly involved in cell cycle/division-related, RNA processing (degradation/splicing), MYC targets and the MTORC1 pathways. In addition, RNA interference (RNAi)-mediated MRPL13 silencing remarkedly inhibited proliferation and migration as well as the expression of EMT-related genes of BC cells in vitro. Mechanistically, attenuation of MRPL13 significantly suppressed the phosphorylation of AKT and mTOR, which could be partially abolished by 740Y-P (a PI3K agonist). Conclusion Our results provide evidence for the first time that increased MRPL13 expression correlates with adverse clinicopathological variables and unfavorable clinical outcomes of BC patients. Knockdown of MRPL13 restrains the proliferation and migration potential and EMT process of BC through inhibiting PI3K/AKT/mTOR signaling pathway.

Single-cell transcriptome analysis of diffuse large B cells in cerebrospinal fluid of central nervous system lymphoma

“…EZH2 (enhancer of zeste homolog 2) functions as a transcriptional repressor by methylating H3K27 (histone H3 at lysine 27), whose mutations and over-expression have been shown to be oncogenic and promote tumor progression in many cancers, especially associated with DLBCL deriving from germinal center (GC) B cells ( Chase and Cross, 2011 ; Velichutina et al., 2010 ), although previous study showed up to 96% PCNSLs have similarity with DLBCLs of the activated B-cell (ABC) type ( Hiemcke-Jiwa et al., 2018 ). In addition, the genes PHF19 ( Ning et al., 2018 ), CENPU ( Zhang et al., 2018 ), PKMYT1 ( Schmidt et al., 2017 ), NCAPH2 ( Wallace et al., 2019 ), PTTG1 ( Huang et al., 2018 ), SMC4 ( Steffensen et al., 2001 ), LAS1L ( Castle et al., 2010 ), MRPL ( Cai et al., 2021 ), MYBL2 ( Iness et al., 2019 ), NUSAP1 ( Simonetti et al., 2019 ), PHF6 ( Warmerdam et al., 2020 ), and RRM2 ( Shu et al., 2020 ) play important roles in cell cycle and proliferation. The 24 genes deserve further study due to their expression specificity in CSF-DLBCs.…”

A Novel Mitochondrial-Related Nuclear Gene Signature Predicts Overall Survival of Lung Adenocarcinoma Patients

“…Meanwhile, 18 NMGs significantly correlated with unfavorable prognosis in LUAD patients were identified. Among them, SCO1 , HSPD1 , IARS2 , MRPL44 , TFAM , NDUFS2 , MRPL13 , OPA1 , and YARS have been previously identified as oncogenes in lung cancer or other types of cancers, serving as unfavorable prognosis biomarkers individually ( Telang et al, 2012 ; Lee et al, 2017 ; Sotgia and Lisanti, 2017 ; Di et al, 2019 ; Dunham-Snary et al, 2019 ; Liu et al, 2019 ; Witherspoon et al, 2019 ; Li et al, 2020 ; Zhang et al, 2020 ; Cai et al, 2021 ). However, it is noteworthy that nearly all these findings were established and assessed in vitro , and all these NMGs were analyzed separately instead of integrating.…”

Identification of the Upregulation of MRPL13 as a Novel Prognostic Marker Associated with Overall Survival Time and Immunotherapy Response in Breast Cancer

“…Mitochondrial ribosomal protein L13 (MRPL13) is located on chromosome 6 and encodes the 39S large subunit of mitochondrial ribosomes [ 31 , 32 ]. MRPL13 is a predictive biomarker of BRCA and exhibits a relationship to the immune infiltration of BRCA.…”

“…MRPL13 is a predictive biomarker of BRCA and exhibits a relationship to the immune infiltration of BRCA. MRPL13 mediated the promotion of BRCA cells' proliferation, migration, and EMT process through PI3K-AKT-mTOR pathway [ 32 ]. siRNA-mediated knockout of MRPL13 reduces the expression of mitochondrial protein in SNU387 cells, reduces oxygen consumption, and increases CLN1-mediated tumor cell invasiveness [ 33 – 35 ].…”