CLEC4M is associated with poor prognosis and promotes cisplatin resistance in NSCLC patients
CLEC4M is associated with poor prognosis and promotes cisplatin resistance in NSCLC patients
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DOI：
10.7150/jca.30139
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发表时间：
2019-01-01
影响因子：
3.9
通讯作者：
Liu, Zhao-Qian
中科院分区：
文献类型：
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作者：
Tan, Li-Ming;Li, Xi;Liu, Zhao-Qian
以顺铂为主的化疗是治疗主要非小细胞肺癌(NSCLC)患者的基础。然而，顺铂耐药仍然是一个具有挑战性的问题，这种耐药的分子机制仍有待充分探讨。CLEC4M是一种依赖于钙离子的C型凝集素，最近被发现与肿瘤的发生有关。本研究主要探讨CLEC4M是否影响临床预后，以及CLEC4M在非小细胞肺癌顺铂耐药中的作用。我们的结果发现，CLEC4M与肺癌患者的预后不良有关。此外，CLEC4M的表达与顺铂的IC50值呈正相关，提示CLEC4M可能影响顺铂的敏感性。体外培养的A549和H1299细胞的实验结果证实，CLEC4M可以增强顺铂的耐药性，而CLEC4M基因敲除导致这些细胞对顺铂的敏感性增加。进一步的实验表明，CLEC4M抑制顺铂诱导的细胞凋亡，并通过上调XPA和ERCC1的表达来提高DNA修复能力。此外，无论有无顺铂治疗，CLEC4M均能促进细胞迁移。总之，这些发现提示CLEC4M抑制在克服非小细胞肺癌患者顺铂耐药方面的潜在临床意义。
Cisplatin-based chemotherapy is the foundation of treatment for major non-small cell lung cancer (NSCLC) patients. However, cisplatin resistance is still a challenging issue, and the molecular mechanisms underlying this resistance remain to be fully explored. CLEC4M, a Ca2+-dependent C-type lectin, has recently been found to correlate with tumourigenesis. This study mainly focused on whether CLEC4M impacts clinical prognosis and how CLEC4M contributes to cisplatin resistance in NSCLC. Our results found that CLEC4M was correlated with poor prognosis in patients with lung cancer. In addition, a positive association between CLEC4M expression and the IC50 values of cisplatin was found, which suggests that CLEC4M may impact cisplatin sensitivity. In vitro results from cultured A549 and H 1299 cells confirmed that CLEC4M could enhance cisplatin resistance, while CLEC4M knockdown led to higher sensitivity to cisplatin in these cells. Further experiments showed that the underlying mechanisms included inhibition of cisplatin-induced cell apoptosis by CLEC4M and improved DNA repair capacity by upregulating XPA and ERCC1 expression. In addition, CLEC4M was able to promote cell migration with or without cisplatin treatment. Collectively, these findings suggest the potential clinical significance of CLEC4M inhibition in overcoming cisplatin resistance in NSCLC patients.