Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China.
Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, China.
Reprod Sci. 2023 Feb;30(2):601-614. doi: 10.1007/s43032-022-01042-6. Epub 2022 Aug 4.
Cervical cancer is a common malignancy that affects women worldwide. The long non-coding RNA (lncRNA) urothelial cancer-associated 1a (UCA1a) is reported to be significantly upregulated in cervical cancer. However, the exact role of UCA1a in cervical cancer remains unknown. This study aimed to identify two core promoter regions in UCA1a, which are essential for CEBPA-dependent transcription and FOXL1-, FOXL4-, and FOXL6-dependent activation, respectively. RNA sequencing results showed that overexpression of UCA1a resulted in extensive changes in the gene expression profile of HeLa cells, especially in the signaling pathway that regulates tumorgenesis. Mass spectrometry assay was conducted to show that pyruvate kinase M2 (PKM2) was a UCA1a-interacting protein. The 400 ~ 800 nt long region of UCA1a at the 5' end and the A1B domain of PKM2 were critical for the UCA1a-PKM2 interaction. Functional assays were performed to show that PKM2 was sufficient and necessary for UCA1a-induced proliferation of HeLa cells, which was partly due to the regulating of nuclear translocation and stabilization of PKM2. These findings provide a novel mechanism for UCA1a to regulate Hela cells by ubiquitination degradation of PKM2 and suggest that UCA1a may play a key role in the progression of cervical cancer.
宫颈癌是一种常见的恶性肿瘤，影响着全世界的女性。研究报道，长链非编码 RNA（lncRNA）尿路上皮癌相关 1a（UCA1a）在宫颈癌中显著上调。然而，UCA1a 在宫颈癌中的确切作用仍不清楚。本研究旨在鉴定 UCA1a 中的两个核心启动子区域，它们分别是 CEBPA 依赖性转录和 FOXL1、FOXL4 和 FOXL6 依赖性激活所必需的。RNA 测序结果表明，UCA1a 的过表达导致 HeLa 细胞的基因表达谱发生广泛变化，特别是在调节肿瘤发生的信号通路中。质谱分析实验表明，丙酮酸激酶 M2（PKM2）是 UCA1a 的相互作用蛋白。UCA1a 在 5'端的 400~800nt 长区域和 PKM2 的 A1B 结构域对于 UCA1a-PKM2 相互作用至关重要。功能实验表明，PKM2 对于 UCA1a 诱导的 HeLa 细胞增殖是充分和必要的，这部分是由于 PKM2 的核转位和稳定的调节。这些发现为 UCA1a 通过泛素化降解 PKM2 调节 Hela 细胞提供了一个新的机制，并表明 UCA1a 可能在宫颈癌的进展中发挥关键作用。
