Huang Yun, Feng Mudan, Jiang Yiwei, Wang Maihuan, Wang Mingkun, Cao Zhen
Department of General Surgery, The Sixth Medical Center, Chinese PLA General Hospital, Beijing, China.
Department of Emergency, The Seventh Medical Centre, Chinese PLA General Hospital, Beijing, China.
Cancer Gene Ther. 2025 Jul 24. doi: 10.1038/s41417-025-00943-3.
Breast cancer (BC) remains a leading cause of cancer-related mortality, largely due to its aggressive proliferation and metastatic potential. Long non-coding RNAs (lncRNAs) have emerged as key regulators in tumor development and progression. This study explored the functional role and mechanism of Lnc-PRSS23-AS1 in BC. We assessed Lnc-PRSS23-AS1 expression and localization using fluorescence in situ hybridization, qRT-PCR, and Western blotting in BC tissues and cell lines. Binding interactions between Lnc-PRSS23-AS1, miR-3176, and Y-box binding protein 1 (YBX1) were validated through dual-luciferase reporter assays, RNA pulldown, and RNA immunoprecipitation. Lnc-PRSS23-AS1 was significantly upregulated in BC and predominantly localized in the cytoplasm. Silencing Lnc-PRSS23-AS1 or overexpressing miR-3176 suppressed BC cell proliferation, migration, and invasion in vitro and in vivo. Conversely, miR-3176 inhibition or YBX1 overexpression reversed these effects. Mechanistically, Lnc-PRSS23-AS1 promoted YBX1 protein expression by acting as a molecular sponge for miR-3176. These findings highlight the Lnc-PRSS23-AS1/miR-3176/YBX1 axis as a driver of BC progression and suggest Lnc-PRSS23-AS1 as a potential therapeutic target for breast cancer treatment.
乳腺癌（BC）仍然是癌症相关死亡的主要原因，这在很大程度上归因于其侵袭性增殖和转移潜能。长链非编码RNA（lncRNAs）已成为肿瘤发生和进展的关键调节因子。本研究探讨了Lnc-PRSS23-AS1在乳腺癌中的功能作用及机制。我们通过荧光原位杂交、qRT-PCR和蛋白质免疫印迹法评估了乳腺癌组织和细胞系中Lnc-PRSS23-AS1的表达及定位。通过双荧光素酶报告基因检测、RNA下拉实验和RNA免疫沉淀验证了Lnc-PRSS23-AS1、miR-3176和Y盒结合蛋白1（YBX1）之间的结合相互作用。Lnc-PRSS23-AS1在乳腺癌中显著上调，且主要定位于细胞质中。沉默Lnc-PRSS23-AS1或过表达miR-3176在体外和体内均抑制了乳腺癌细胞的增殖、迁移和侵袭。相反，抑制miR-3176或过表达YBX1可逆转这些效应。机制上，Lnc-PRSS23-AS1通过充当miR-3176的分子海绵促进YBX1蛋白表达。这些发现突出了Lnc-PRSS23-AS1/miR-3176/YBX1轴作为乳腺癌进展的驱动因素，并提示Lnc-PRSS23-AS1作为乳腺癌治疗的潜在靶点。
