Depletion of MRPL35 inhibits gastric carcinoma cell proliferation by regulating downstream signaling proteins

被引:14
作者
Yuan, Ling [1 ,2 ]
Li, Jia-Xin [1 ]
Yang, Yi [1 ]
Chen, Yan [3 ]
Ma, Ting-Ting [1 ]
Liang, Shuang [4 ]
Bu, Yang [5 ]
Yu, Lei [6 ]
Nan, Yi [2 ]
机构
[1] Ningxia Med Univ, Pharm Coll, Yinchuan 750004, Ningxia, Peoples R China
[2] Ningxia Med Univ, Minist Educ, Key Lab Hui Ethn Med Modernizat, 1160 Shengli St, Yinchuan 750004, Ningxia, Peoples R China
[3] Ningxia Med Univ, Tradit Chinese Med Coll, Yinchuan 750004, Ningxia, Peoples R China
[4] Ningxia Med Univ, Dept Oncol & Endocrinol, Yinchuan Hosp Tradit Chinese Med, Yinchuan 750004, Ningxia, Peoples R China
[5] Ningxia Med Univ, Dept Hepatobiliary Surg, Gen Hosp, Yinchuan 750004, Ningxia, Peoples R China
[6] Harbin Med Univ, Dept Infect Dis, Hosp 4, Harbin 150001, Heilongjiang, Peoples R China
关键词
Gastric carcinoma; MRPL35; Apoptosis; Proliferation; Tissue microarray; Isobaric tags for relative and absolute quantification; APOPTOSIS; SUBUNIT;
D O I
10.3748/wjg.v27.i16.1785
中图分类号
R57 [消化系及腹部疾病];
学科分类号
100201 [内科学];
摘要
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 public tumor database UALCAN (www.ualcan.path.uab.edu). The effect of the expression of MRPL35 on the prognosis was evaluated with KMplot (www.kmplot.com). The expression of MRPL35 was assessed on the tissue microarray by immunohistochemistry and the level of MRPL35 mRNA in 25 pairs of clinical GC tissues and matched adjacent tissues was detected by quantitative reverse transcription-polymerase chain reaction. Celigo cell count assay, colony formation assay, and flow cytometry were used to assess the role of MRPL35 in GC cell proliferation and apoptosis in vitro. Additionally, tumor formation experiment in BALB/c nude mice was utilized to determine the effect of MRPL35 on GC cell proliferation. After knockdown of MRPL35, related proteins were identified by isobaric tags for relative and absolute quantification analysis, and the expression of related proteins was detected by Western blot. RESULTS The expression of MRPL35 was up-regulated in GC (P = 1.77 x 10(-4)). The Kaplan-Meier plots of the overall survival indicated that high expression of MRPL35 was associated with a poor survival in GC. Compared with adjacent tissues, the expression 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-metastasis stage (P = 0.024). Knockdown of MRPL35 inhibited GC cell proliferation and colony formation and induced apoptosis. Animal experiment results showed that knockdown of MRPL35 inhibited tumor formation in BALB/c nude mice. Western blotting analysis showed that after knockdown of MRPL35, the expression of PICK1 and BCL-XL proteins decreased, and that of AGR2 protein increased. CONCLUSION Collectively, our findings demonstrate that knockdown of MRPL35 inhibits GC cell proliferation through related proteins including PICK1, BCL-XL, and AGR2.
引用
收藏
页码:1785 / 1804
页数:20
相关论文
共 22 条
[1]
Identification of Crucial Candidate Genes and Pathways in Glioblastoma Multiform by Bioinformatics Analysis [J].
Alshabi, Ali Mohamed ;
Vastrad, Basavaraj ;
Shaikh, Ibrahim Ahmed ;
Vastrad, Chanabasayya .
BIOMOLECULES, 2019, 9 (05)
[2]
MrpL35, a mitospecific component of mitoribosomes, plays a key role in cytochrome c oxidase assembly [J].
Box, Jodie M. ;
Kaur, Jasvinder ;
Stuart, Rosemary A. .
MOLECULAR BIOLOGY OF THE CELL, 2017, 28 (24) :3489-3499
[3]
Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI [10.3322/caac.21492, 10.3322/caac.21609]
[4]
Structure of the large ribosomal subunit from human mitochondria [J].
Brown, Alan ;
Amunts, Alexey ;
Bai, Xiao-chen ;
Sugimoto, Yoichiro ;
Edwards, Patricia C. ;
Murshudov, Garib ;
Scheres, Sjors H. W. ;
Ramakrishnan, V. .
SCIENCE, 2014, 346 (6210) :718-722
[5]
Buchynska L. G., 2018, Experimental Oncology, V40, P303
[6]
Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods [J].
Ferlay, J. ;
Colombet, M. ;
Soerjomataram, I. ;
Mathers, C. ;
Parkin, D. M. ;
Pineros, M. ;
Znaor, A. ;
Bray, F. .
INTERNATIONAL JOURNAL OF CANCER, 2019, 144 (08) :1941-1953
[7]
Down-regulation of MRPS23 inhibits rat breast cancer proliferation and metastasis [J].
Gao, Yan ;
Li, Fuyan ;
Zhou, Hong ;
Yang, Yi ;
Wu, Ruimin ;
Chen, Yijia ;
Li, Wei ;
Li, Yang ;
Xu, Xueqin ;
Ke, Changbin ;
Pei, Zhijun .
ONCOTARGET, 2017, 8 (42) :71772-71781
[8]
Mammalian mitochondrial ribosomal small subunit (MRPS) genes: A putative role in human disease [J].
Gopisetty, Gopal ;
Thangarajan, Rajkumar .
GENE, 2016, 589 (01) :27-35
[9]
Mitochondrial ribosomal protein L41 mediates serum starvation-induced cell-cycle arrest through an increase of p21WAF1/CIP1 [J].
Kim, MJ ;
Yoo, YA ;
Kim, HJ ;
Kang, S ;
Kim, YG ;
Kim, JS ;
Yoo, YD .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 338 (02) :1179-1184
[10]
Integrated molecular portrait of non-small cell lung cancers [J].
Lazar, Vladimir ;
Suo, Chen ;
Orear, Cedric ;
van den Oord, Joost ;
Balogh, Zsofia ;
Guegan, Justine ;
Job, Bastien ;
Meurice, Guillaume ;
Ripoche, Hugues ;
Calza, Stefano ;
Hasmats, Johanna ;
Lundeberg, Joakim ;
Lacroix, Ludovic ;
Vielh, Philippe ;
Dufour, Fabienne ;
Lehtio, Janne ;
Napieralski, Rudolf ;
Eggermont, Alexander ;
Schmitt, Manfred ;
Cadranel, Jacques ;
Besse, Benjamin ;
Girard, Philippe ;
Blackhall, Fiona ;
Validire, Pierre ;
Soria, Jean-Charles ;
Dessen, Philippe ;
Hansson, Johan ;
Pawitan, Yudi .
BMC MEDICAL GENOMICS, 2013, 6