Ovarian cancer remains the sixth most frequently occurring cancer in women worldwide. Long noncoding RNAs (lncRNAs) are capable of regulating gene expression, and thus, participating in a wide range of biological functions and disease processes including cancer development. Our work suggests that lncRNA TMPO antisense RNA 1 (TMPO‐AS1) represents an oncogenic lncRNA in ovarian cancer and presents a novel mechanism involving transcription factor E2F transcription factor 6 (E2F6) and lipocalin‐2 (LCN2). We identified upregulated lncRNA TMPO‐AS1 in ovarian cancer tissues and cells. siRNA‐mediated silencing of lncRNA TMPO‐AS1 restrained the aggressiveness of ovarian cancer cells and their pro‐angiogenic ability, and reduced the expression of LCN2. LncRNA TMPO‐AS1 was found to interact with E2F6, a transcriptional repressor that could bind to the promoter region of LCN2 gene. In addition, silencing of E2F6 or overexpression of LCN2 restored the aggressiveness of ovarian cancer cells and their pro‐angiogenic ability following siRNA‐mediated silencing of lncRNA TMPO‐AS1. Taken together, we demonstrated lncRNA TMPO‐AS1 could potentially promote LCN2 transcriptional activity by binding to transcription factor E2F6, and thus, stimulated the progression of ovarian cancer. These findings underscore a possible alternative therapeutic strategy for ovarian cancer treatment.

中文翻译：

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LncRNA TMPO-AS1促进LCN2转录活性并在卵巢癌中发挥致癌作用

卵巢癌仍然是全球女性中第六大最常见的癌症。长链非编码 RNA (lncRNA) 能够调节基因表达，从而参与广泛的生物学功能和疾病过程，包括癌症的发展。我们的工作表明 lncRNA TMPO 反义 RNA 1 (TMPO-AS1) 代表了卵巢癌中的致癌 lncRNA，并提出了一种涉及转录因子 E2F 转录因子 6 (E2F6) 和脂质运载蛋白 2 (LCN2) 的新机制。我们在卵巢癌组织和细胞中发现了上调的 lncRNA TMPO-AS1。siRNA介导的lncRNA TMPO-AS1沉默抑制了卵巢癌细胞的侵袭性及其促血管生成能力，并降低了LCN2的表达。发现 LncRNA TMPO-AS1 与 E2F6 相互作用，一种可以与 LCN2 基因启动子区域结合的转录阻遏物。此外，在siRNA介导的lncRNA TMPO-AS1沉默后，E2F6的沉默或LCN2的过表达恢复了卵巢癌细胞的侵袭性及其促血管生成能力。总之，我们证明了 lncRNA TMPO-AS1 可能通过与转录因子 E2F6 结合来促进 LCN2 转录活性，从而刺激卵巢癌的进展。这些发现强调了一种可能的卵巢癌治疗替代治疗策略。我们证明了 lncRNA TMPO-AS1 可能通过与转录因子 E2F6 结合来促进 LCN2 转录活性，从而刺激卵巢癌的进展。这些发现强调了卵巢癌治疗的一种可能的替代治疗策略。我们证明了 lncRNA TMPO-AS1 可能通过与转录因子 E2F6 结合来促进 LCN2 转录活性，从而刺激卵巢癌的进展。这些发现强调了卵巢癌治疗的一种可能的替代治疗策略。