Investigation on a competitive endogenous RNA (ceRNA) network attracted lots of attention due its function in cancer regulation. Here, we probed into the possible molecular mechanism of circSSPO/microRNA-6820-5p (miR-6820-5p)/kallikrein-related peptidase 8 (KLK8)/PKD1 network in the esophageal squamous cell carcinoma (ESCC). Following whole-transcriptome sequencing and differential analysis in collected ESCC tissue samples, circRNA-miRNA-mRNA regulatory network affecting ESCC was investigated. After interaction measurement among circSSPO/miR-6820-5p/KLK8/PKD1, their regulatory roles in ESCC cell functions in vitro and xenograft tumor growth and lung metastasis in vivo were analyzed. The bioinformatics prediction and sequencing results screened that circSSPO, miR-6820-5p, KLK8, and PKD1 were associated with ESCC development. In ESCC, miR-6820-5p was expressed at very low levels, while circSSPO, KLK8, and PKD1 were highly expressed. In vitro cell experiments further proved that circSSPO competitively inhibited miR-6820-5p to induce ESCC cell malignant properties. Moreover, knockdown of KLK8 or PKD1 inhibited ESCC cell malignant properties. circSSPO also promoted the tumorigenic and metastasis of ESCC through the upregulation of KLK8 and PKD1 expression in vivo. We found that circSSPO was an oncogenic circRNA that was significantly abundant in ESCC tissues and circSSPO exhibited an oncogenic activity in ESCC by elevating expression of KLK8 and PKD1 through suppressing miR-6820-5p expression.

竞争性内源性 RNA (ceRNA) 网络的研究因其在癌症调节中的功能而引起了广泛关注。在此，我们探讨了circSSPO/microRNA-6820-5p（miR-6820-5p）/激肽释放酶相关肽酶8（KLK8）/PKD1网络在食管鳞状细胞癌（ESCC）中的可能分子机制。对收集的 ESCC 组织样本进行全转录组测序和差异分析后，研究了影响 ESCC 的 circRNA-miRNA-mRNA 调控网络。在测量circSSPO/miR-6820-5p/KLK8/PKD1之间的相互作用后，分析它们在体外对ESCC细胞功能和体内异种移植肿瘤生长和肺转移中的调节作用。生物信息学预测和测序结果筛选出circSSPO、miR-6820-5p、KLK8、PKD1与ESCC的发生相关。在 ESCC 中，miR-6820-5p 的表达水平非常低，而 circSSPO、KLK8 和 PKD1 的表达水平很高。体外细胞实验进一步证明，circSSPO竞争性抑制miR-6820-5p诱导ESCC细胞恶性特性。此外，敲除 KLK8 或 PKD1 可以抑制 ESCC 细胞的恶性特性。circSSPO还通过体内上调KLK8和PKD1表达促进ESCC的致瘤和转移。我们发现circSSPO是一种致癌circRNA，在ESCC组织中显着丰富，并且circSSPO通过抑制miR-6820-5p表达来升高KLK8和PKD1的表达，从而在ESCC中表现出致癌活性。