Aberrant expression of meiosis-specific genes in cancer has recently emerged as a driver of some cancer formation. Aurora kinase C (AURKC) is a member of the Aurora kinase family of proteins known to regulate chromosome segregation during cell divisions. AURKC is normally expressed in meiotic cells; however, elevated levels of AURKC mRNA and protein are frequently measured in cancer cells. To understand the function of AURKC in cancer cells, expression was induced in noncancerous, human retina pigmented epithelial cells. While AURKC expression did not alter cell proliferation over 72 h, it did increase cell migration and anchorage independent growth in soft agar suggesting an oncogenic role in mitotically dividing cells. To evaluate AURKC as a potential therapeutic target, a frameshift mutation in the gene was introduced in U2OS osteosarcoma cells using CRISPR-Cas9 technology resulting in a premature stop codon. Cancer cells lacking AURKC displayed no change in cell proliferation over 72 h but did migrate less and formed fewer colonies in soft agar. Whole transcriptome sequencing analysis uncovered over 400 differentially expressed genes in U2OS cells with and without AURKC. GO analysis revealed alterations in proteinaceous extracellular matrix genes including COL1A1. These data indicate that therapeutics targeting AURKC could decrease cancer cell metastasis and disease progression. Because AURKC is transcriptionally silenced in normal mitotic cells, its disruption could specifically target cancer cells limiting the toxic side effects associated with current therapeutics.

癌症中减数分裂特异性基因的异常表达最近已成为某些癌症形成的驱动因素。极光激酶 C (AURKC) 是已知在细胞分裂过程中调节染色体分离的蛋白质极光激酶家族的成员。AURKC通常在减数分裂细胞中表达；然而，在癌细胞中经常测量到AURKC mRNA 和蛋白质水平升高。为了了解AURKC在癌细胞中的功能，在非癌性人视网膜色素上皮细胞中诱导表达。而AURKC表达在 72 小时内没有改变细胞增殖，它确实增加了软琼脂中的细胞迁移和贴壁独立生长，表明在有丝分裂细胞中具有致癌作用。为了评估 AURKC 作为潜在治疗靶点，使用 CRISPR-Cas9 技术将基因移码突变引入 U2OS 骨肉瘤细胞，导致过早终止密码子。缺乏AURKC 的癌细胞在 72 小时内的细胞增殖没有变化，但迁移较少，在软琼脂中形成的集落较少。全转录组测序分析在有和没有AURKC 的U2OS 细胞中发现了 400 多个差异表达的基因。GO 分析揭示了包括COL1A1在内的蛋白质细胞外基质基因的改变。这些数据表明，靶向AURKC 的疗法可以减少癌细胞转移和疾病进展。由于AURKC在正常有丝分裂细胞中被转录沉默，它的破坏可以专门针对癌细胞，从而限制与当前疗法相关的毒副作用。