The Novel Methylation Biomarker SCARA5 Sensitizes Cancer Cells to DNA Damage Chemotherapy Drugs in NSCLC

作者全名："Peng, Qi; Liu, Yan; Kong, Xuehua; Xian, Jie; Ye, Lin; Yang, Li; Guo, Shuliang; Zhang, Yan; Zhou, Lan; Xiang, Tingxiu"

作者地址："[Peng, Qi; Liu, Yan; Kong, Xuehua; Zhang, Yan; Zhou, Lan] Chongqing Med Univ, Key Lab Diagnost Med, Minist Educ, Chongqing, Peoples R China; [Peng, Qi; Liu, Yan; Kong, Xuehua; Zhang, Yan; Zhou, Lan] Chongqing Med Univ, Sch Lab Med, Chongqing, Peoples R China; [Xian, Jie; Ye, Lin; Xiang, Tingxiu] Chongqing Med Univ, Key Lab Mol Oncol & Epigenet, Affiliated Hosp 1, Chongqing, Peoples R China; [Yang, Li; Guo, Shuliang] Chongqing Med Univ, Dept Resp & Crit Care Med, Affiliated Hosp 1, Chongqing, Peoples R China"

通信作者："Zhou, L (corresponding author), Chongqing Med Univ, Key Lab Diagnost Med, Minist Educ, Chongqing, Peoples R China.; Zhou, L (corresponding author), Chongqing Med Univ, Sch Lab Med, Chongqing, Peoples R China.; Xiang, TX (corresponding author), Chongqing Med Univ, Key Lab Mol Oncol & Epigenet, Affiliated Hosp 1, Chongqing, Peoples R China."

来源：FRONTIERS IN ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000662963100001

JCR分区：Q2

影响因子：4.7

年份：2021

卷号：11

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：tumor marker; SCARA5; CpG methylation; FOXM1; non-small cell lung cancer

摘要："Background Scavenger Receptor Class A Member 5 (SCARA5), also known as TESR, is expressed in various tissues and organs and participates in host defense. Recent studies have found SCARA5 to produce an anti-tumor effect for multiple tumors, although the mechanistic basis for the effect is unknown. Methods Bioinformatics, methylation-specific polymerase chain reaction (MSP), quantitative real-time PCR, and immunohistochemistry were used to assess promoter methylation and expression of SCARA5 in lung cancer tissues and cell lines. The biological effect of SCARA5 on lung cancer cells was confirmed by the CCK8 assay, colony formation assay, and flow cytometry. GSEA, Western blot, RNA sequencing, and luciferase-based gene reporter assay were used to explore the mechanistic basis for the anti-tumor effect of SCARA5. Chemosensitivity assays were used to evaluate the anti-tumor effect of SCARA5 in conjunction with chemotherapeutic drugs. Results We found SCARA5 to be downregulated in lung cancer cell lines and tissues with SCARA5 levels negatively related to promoter methylation. Ectopic expression of SCARA5 suppressed proliferation of lung cancer both in vitro and in vivo through upregulation of HSPA5 expression, which inhibited FOXM1 expression resulting in G2/M arrest of the A549 cell line. SCARA5 also improved susceptibility of A549 cells to chemotherapeutic drugs that damage DNA. Conclusion SCARA5 was silenced in NSCLC due to promoter methylation and could be a potential tumor marker in NSCLC."

基金机构："National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81872380, 81572769]; Natural Science Foundation of ChongqingNatural Science Foundation of Chongqing [CYB19161]; Key Laboratory of Molecular Oncology and Epigenetics [2019-07]"

基金资助正文："This study was supported by National Natural Science Foundation of China (#81872380, #81572769), Natural Science Foundation of Chongqing (CYB19161), and open fund of Key Laboratory of Molecular Oncology and Epigenetics (2019-07)."