The Novel Methylation Biomarker SCARA5 Sensitizes Cancer Cells to DNA Damage Chemotherapy Drugs in NSCLC.
The Novel Methylation Biomarker SCARA5 Sensitizes Cancer Cells to DNA Damage Chemotherapy Drugs in NSCLC.
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新型甲基化生物标志物 SCARA5 使 NSCLC 中的癌细胞对 DNA 损伤化疗药物敏感
DOI：
10.3389/fonc.2021.666589
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发表时间：
2021
影响因子：
4.7
通讯作者：
Xiang T
中科院分区：
文献类型：
--
作者：
Peng Q;Liu Y;Kong X;Xian J;Ye L;Yang L;Guo S;Zhang Y;Zhou L;Xiang T
背景清道夫受体A类成员5(SCARA5)又称TESR，表达于多种组织器官，参与宿主防御。最近的研究发现，SCARA5对多种肿瘤具有抗肿瘤作用，但这种作用的机制尚不清楚。方法应用生物信息学、甲基化特异性聚合酶链式反应(MSP)、实时荧光定量聚合酶链式反应和免疫组织化学方法检测肺癌组织和细胞系中SCARA5基因启动子甲基化和表达情况。CCK8实验、集落形成实验和流式细胞仪检测证实了SCARA5对肺癌细胞的生物学作用。通过GSEA、Western印迹、RNA测序和基于荧光素酶的基因报告实验，探讨SCARA5抗肿瘤作用的机制。采用药敏试验评价SCARA5联合化疗药物的抗肿瘤作用。结果我们发现SCARA5在肺癌细胞系和肺癌组织中表达下调，且SCARA5水平与启动子甲基化呈负相关。异位表达SCARA5通过上调HSPA5的表达抑制肺癌细胞的增殖，从而抑制FOXM1的表达，使A549细胞发生G2/M期停滞。SCARA5还提高了A549细胞对破坏DNA的化疗药物的敏感性。结论SCARA5在非小细胞肺癌中由于启动子甲基化而沉默，可能成为非小细胞肺癌的一种潜在的肿瘤标志物。
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.
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影响因子：
3
作者：
Jang, JoungSoon;Kim, Hoon-Kyo;Shin, Jong Wook
通讯作者：
Shin, Jong Wook
影响因子：
11.8
作者：
Li, Jau Yi;Paragas, Neal;Ned, Renee M.;Qiu, Andong;Viltard, Melanie;Leete, Thomas;Drexler, Ian R.;Chen, Xia;Sanna-Cherchi, Simone;Mohammed, Farah;Williams, David;Lin, Chyuan Sheng;Schmidt-Ott, Kai M.;Andrews, Nancy C.;Barasch, Jonathan
通讯作者：
Barasch, Jonathan
影响因子：
5.2
作者：
Rundle S;Bradbury A;Drew Y;Curtin NJ
通讯作者：
Curtin NJ
影响因子：
8.8
作者：
Haßdenteufel S;Johnson N;Paton AW;Paton JC;High S;Zimmermann R
通讯作者：
Zimmermann R
影响因子：
51.1
作者：
Mitsudomi, Tetsuya;Morita, Satoshi;Fukuoka, Masahiro
通讯作者：
Fukuoka, Masahiro