SMYD2 promotes tumorigenesis and metastasis of lung adenocarcinoma through RPS7

Abstract

The protein methyltransferase SET and MYND domain-containing protein 2 (SMYD2) is a transcriptional regulator that methylates histones and nonhistone proteins. As an oncogene, SMYD2 has been investigated in numerous types of cancer. However, its involvement in lung cancer remains elusive. The prognostic value of SMYD2 expression in lung adenocarcinoma (LUAD) was determined through bioinformatics analysis, reverse-transcription polymerase chain reaction, western blotting, and immunohistochemistry. The effect of SMYD2 on LUAD cell proliferation and metastasis was explored in vivo and in vitro, and the underlying mechanisms were investigated via RNA-seq, and chromatin immunoprecipitation-quantitative PCR. SMYD2 expression was significantly upregulated in LUAD cell lines and tissues. High SMYD2 expression was associated with shorter overall and disease-free survival in LUAD patients. Inhibition of SMYD2 with SMYD2 knockdown or AZ505 dramatically inhibited the proliferation, migration, and invasion ability of GLC-82 and SPC-A1 cells and remarkably reduced tumor growth in mice. Mechanically, SMYD2 may activate the transcription of ribosomal small subunit protein 7 (RPS7) by binding to its promoter. Following overexpression of SMYD2, the proliferation, migration, and invasion of cells increased, which was partially reversed by RPS7. Thus, SMYD2 might modulate tumorigenesis and metastasis mediated by RPS7 LUAD. SMYD2 might be a prognostic biomarker and therapeutic target in LUAD.

Identification of Potential Biomarkers for Progression and Prognosis of Bladder Cancer by Comprehensive Bioinformatics Analysis

“…SMYD2 expression was found to be highly upregulated in lung adenocarcinoma, and high SMYD2 expression was linked to shorter overall and disease-free survival. Mechanically, SMYD2 may promote carcinogenesis and metastasis by activating RPS7 transcription through binding to its promoter [ 24 ]. Inhibition of SMYD2 expression has been shown to significantly reduce cervical cancer proliferation in vivo and in vitro [ 25 ].…”

Identification of RPS7 as the Biomarker of Ferroptosis in Acute Kidney Injury

“…RPS7, in its full name small ribosomal protein subunit 7, is an essential part of the small subunit of ribosomes, and it participates in the bioprocess of protein synthesis in normal states [ 29 ]. Previous publications revealed that RPS7 is involved in the progression of various malignancies, such as prostate cancer and lung cancer [ 29 , 30 ], but its role in renal injuries and ferroptosis has not been investigated. TRIB3, in its full name tribbles pseudokinase 3, was reported to play a pivotal role in cellular stress response [ 31 ].…”

Mechanistic and functional extrapolation of SET and MYND domain-containing protein 2 to pancreatic cancer

“…One study aimed to investigate the function of SMYD2 in PDAC using mouse and cellular models found evidence that SMYD2 plays a pivotal role in the development of this deadly pancreatic cancer[ 16 ] (Figure 1B ). In other human cancers, SMYD2 usually exerts its tumorigenic effects through methylating cell signaling-related proteins and through the effect of such methylation on the targets’ activity, stability, or subcellular localization[ 13 , 27 , 42 , 48 ]. Such a methylation-oriented mechanism has been instrumental for the initial development of a mechanistic hypothesis of SMYD2 involvement in PDAC and for the subsequent success of establishing a novel link of SMYD2 to promoting PDAC growth and progression[ 16 ].…”

“…These pathways include the critical signaling cascade RTK/Ras, the downstream signaling cascades of the RTK/Ras pathway, such as the mitogen-activated protein kinase (MAPK) pathway, and the PI3K/AKT pathway[ 16 , 27 , 28 , 30 , 31 ]. As dysregulation of these signaling pathways is an almost universal phenomenon in cancer, it is not surprising that SMYD2 overexpression has been linked with tumor development and progression in multiple human cancers, such as gastric cancer[ 33 ], esophageal squamous cell carcinoma[ 34 ], breast cancer[ 30 ], bladder cancer[ 23 ], colon cancer[ 31 , 35 ], colorectal cancer[ 36 ], hepatocellular carcinoma[ 14 ], acute lymphoblastic leukemia[ 37 , 38 ], hematopoietic leukemias[ 39 ], head and neck squamous cell carcinoma[ 15 ], lung adenocarcinoma[ 13 ], papillary thyroid carcinoma[ 40 ], cervical cancer[ 41 , 42 ], ovarian clear cell carcinoma[ 43 , 44 ], and renal cell carcinoma[ 45 , 46 ] (Table 2 ).…”