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

Abstract

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 ( ). The effect of the expression of MRPL35 on the prognosis was evaluated with KMplot ( ). 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 × 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 ...

Potential of Mitochondrial Ribosomal Genes as Cancer Biomarkers Demonstrated by Bioinformatics Results

“…MRPL35 expression is upregulated in GC and is associated with a poor prognosis. Cell functional studies have revealed that the knockdown of MRPL35 inhibits cell proliferation in GC via related proteins, including PICK1, Bcl-xL, and AGR2 (84). High expression of MRPS29 in GC is associated with a better prognosis, and the downregulation of MRPS29 expression could increase resistance to chemotherapy by inhibiting apoptosis and promoting cell migration, consistent with the pro-apoptotic function of MRPS29 (85).…”

Knockdown of MRPL35 promotes cell apoptosis and inhibits cell proliferation in non-small-cell lung cancer

“…The down-regulated expression of MRPL35 can increase reactive oxygen species (ROS) levels, correlating with DNA damage [ 23 ]. Increased ROS levels may lead to more extensive and irreparable cell damage via DNA oxidation [ 24 , 25 ].…”

Identification and validation of a fatty acid metabolism gene signature for the promotion of metastasis in liver cancer

“…After filtering using the LASSO algorithm, three core genes remained: PLCD3, MRPL35 and CYP2S1. Studies have reported the tumor-promotive role of PLCD3 in thyroid cancer ( 32 ) and osteosarcoma ( 33 ), the role of MRPL35 in gastric ( 34 ) and colorectal ( 35 ) cancer, and the role of CYP2S1 in breast ( 36 ) and lung ( 37 ) cancer. Consistent with this, the group with high WF scores, calculated for the three genes, showed significantly worse outcomes compared with those with low WF scores.…”