Table_1_RETRACTED: Circular RNA circ-0016068 Promotes the Growth, Migration, and Invasion of Prostate Cancer Cells by Regulating the miR-330-3p/BMI-1 Axis as a Competing Endogenous RNA.pdf

Prostate cancer is a common neoplasm worldwide, and the sixth most common cause of cancer-related mortality. Biomarkers for earlier diagnosis and improved treatment alternatives are critical. Circular RNAs (circRNAs) can promote the growth and progression of various cancers; however, prostate cancer-specific circRNAs have not been found. We identified circ-0016068, a circRNA that was expressed more strongly in prostate cancer tumors vs. normal paired tissue, and confirmed its relatively high expression in prostate cancer tissues and cell lines. We also discerned that circ-0016068 promotes the epithelial-to-mesenchymal transition (EMT) and the growth, migration, and invasion of prostate cancer cells in vitro; and promotes the growth and metastasis of tumors in a mouse model of prostate cancer. Moreover, we found that circ-0016068 competes with the B-lymphoma Moloney murine leukemia virus insertion region-1 (BMI-1) for binding to miR-330-3p. In so doing, circ-0016068 sequesters miR-330-3p and frees BMI-1 to enhance the proliferation, migration, and invasion of prostate cancer cells, and the metastasis of xenograft tumors. These results suggest that circ-0016068 may be a promising diagnostic biomarker for early stage prostate cancer and a potential target for novel cancer therapeutics.

前列腺癌是全球高发的肿瘤性疾病，亦是癌症相关死亡的第六大常见诱因。用于早期诊断与优化治疗策略的生物标志物（biomarker）至关重要。环状RNA（Circular RNAs，circRNAs）可促进多种肿瘤的发生发展，但目前尚未发现前列腺癌特异性的circRNA。我们鉴定出circ-0016068——一种在前列腺癌组织中相较于配对正常组织表达显著上调的环状RNA——并证实其在前列腺癌组织与细胞系中均呈相对高表达水平。此外我们发现，circ-0016068可在体外促进前列腺癌细胞的上皮间质转化（epithelial-to-mesenchymal transition，EMT）、增殖、迁移与侵袭；同时可在前列腺癌小鼠模型中促进肿瘤生长与转移。此外，我们发现circ-0016068可与B细胞淋巴瘤莫洛尼鼠白血病病毒插入区1（B-lymphoma Moloney murine leukemia virus insertion region-1，BMI-1）竞争性结合miR-330-3p。通过这一竞争机制，circ-0016068可隔离miR-330-3p，从而释放BMI-1，以增强前列腺癌细胞的增殖、迁移与侵袭能力，并促进异种移植瘤的转移。上述研究结果表明，circ-0016068有望成为早期前列腺癌的潜在诊断生物标志物，亦可为新型癌症治疗策略提供候选靶点。