在前期基金资助下，我们通过转录本测序结合GEO数据库，筛选出钙结合蛋白S100A11与其假基因S100A11P1、S100A11P2在肺腺癌顺铂耐药株A549/DDP中均明显上调。qPCR进一步证实三者在肺腺癌顺铂耐药株与耐药组织、卵巢癌顺铂耐药株与耐药组织中的表达均明显升高；并且三者含有一些相同的miRNA应答元件(MREs)，可竞争性结合miRNA(miR-145、miR-31)。推测非编码的S100A11P1/P2，通过miRNA海绵吸附机制，在转录后水平调控编码基因S100A11的表达，进而影响顺铂化疗敏感性。S100A11参与铂类化疗耐药的机制未明，已有证据表明，S100A11蛋白与DNA损伤修复的同源重组途径有关，那么该机制是否也介导顺铂耐药性？本项目选择临床常见的肺腺癌与卵巢癌，从细胞和动物水平对上述科学假说进行实验验证，将有助于深化理解顺铂耐药机制。

With the support of the early National Natural Science Foundation (No.81472615), we have screened a pair of pseudogene S100A11P1 and S100A11P2, using RNA-sequencing and GEO data. They are significantly unregulated in lung adenocarcinoma (LUAD) resistant cell line A549/DDP and resistant tissues, and ovarian cancer (OC) resistant cell line SKOV3/DDP and resistant tissues, along with upregulation of encoding gene S100A11, a member of the calcium binding protein family. Bioinformatics analysis revealed that S100A11 and S100A11P1/ P2 sharing same miRNA response elements (MREs), competing binding miRNA, such as miR-145, miR-31. As long noncoding RNAs (lncRNA), we peculated that S100A11P1 and S100A11P2 regulate S100A11 expression, at post-transcriptional level, through a competing endogenous RNAs (ceRNAs) mechanism, which act as miRNA sponges, thereby affecting the chemosensitivity of cisplatin. The mechanism by which S100A11 is involved in platinum-based chemotherapy is unclear. There are sufficient evidences that the S100A11 protein is involved in the homologous recombination pathway of DNA damage repair. Does the mechanism also mediate cisplatin resistance? We choose clinically common LUAD and OC to verify the above scientific hypothesis from the cell and animal level. It is expected to deepen the understanding of cisplatin resistance mechanisms and provide potential therapeutic targets and new molecular markers.