Cadmium is a human carcinogen, which induces cancers by mechanisms that are not fully understood. Induction of oxidative stress, apoptosis resistance, genotoxic effects, and epigenetic modulations have been indicated to regulate cadmium-induced carcinogenesis. Circular RNAs are epigenetic regulators that have been recognized to play essential roles in carcinogenesis. Yet, the involvement of circular RNAs in cadmium carcinogenesis remains unclear. In this study, a novel circular RNA, circPUS7, was identified and described for the first time. CircPUS7 was significantly upregulated at week 12, 16, and 20 during the cadmium-induced transformation of human bronchial epithelial BEAS-2B cells. Knockdown of circPUS7 in cadmium-transformed BEAS-2B (T-BEAS-2B) cells significantly attenuated transformation markers including cell proliferation, migration, invasion, and anchorage-independent growth. Moreover, circPUS7 promoted malignant phenotypes by competitively binding with miR-770. Overexpression of miR-770 significantly inhibited the transformation properties of T-BEAS-2B cells while inhibition of miR-770 potently reversed the inhibitory effects of circPUS7 knockdown in proliferation, migration, invasion, and anchorage-independent growth of the T-BEAS-2B cells. Kirsten rat sarcoma viral oncogene homolog (KRAS), which was increased synchronically with circPUS7 during cadmium-induced cell transformation, was regulated by circPUS7 through sponging miR-770. In summary, our findings demonstrate that circPUS7 promotes cadmium-induced cell transformation through sponging miR-770 to regulate KRAS expression, providing a new perspective with the involvement of circular RNAs to further understand the mechanisms of cadmium carcinogenesis.

中文翻译：

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一种新的环状 RNA，circPUS7 通过海绵化 miR-770 调节 Kirsten 大鼠肉瘤病毒癌基因同源物的表达，促进镉诱导的人支气管上皮细胞转化。

镉是一种人类致癌物，其诱发癌症的机制尚不完全清楚。已表明诱导氧化应激、细胞凋亡抗性、遗传毒性作用和表观遗传调节可调节镉诱导的致癌作用。环状 RNA 是表观遗传调节因子，已被公认为在致癌作用中发挥重要作用。然而，环状 RNA 在镉致癌过程中的作用仍不清楚。在这项研究中，首次鉴定和描述了一种新型环状 RNA circPUS7。在镉诱导的人支气管上皮 BEAS-2B 细胞转化过程中，CircPUS7 在第 12、16 和 20 周显着上调。在镉转化的 BEAS-2B (T-BEAS-2B) 细胞中敲除 circPUS7 显着减弱了转化标志物，包括细胞增殖、迁移、入侵和不依赖锚定的生长。此外，circPUS7 通过与 miR-770 竞争性结合来促进恶性表型。miR-770 的过表达显着抑制了 T-BEAS-2B 细胞的转化特性，而 miR-770 的抑制则有效地逆转了 circPUS7 敲低对 T-BEAS-2B 增殖、迁移、侵袭和锚定非依赖性生长的抑制作用细胞。在镉诱导的细胞转化过程中，与 circPUS7 同步增加的 Kirsten 大鼠肉瘤病毒癌基因同源物 (KRAS) 被 circPUS7 通过海绵状 miR-770 调节。总之，我们的研究结果表明，circPUS7 通过海绵化 miR-770 来调节 KRAS 表达，从而促进镉诱导的细胞转化，