Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.
Cancer Med. 2023 May;12(10):11971-11982. doi: 10.1002/cam4.5872. Epub 2023 Mar 29.
Breast cancer (BC) is the most common malignancy affecting women. It is vital to explore sensitive biological markers to diagnose and treat BC patients. Recent studies have proved that long noncoding RNAs (lncRNAs) were involved in breast tumor progression. Nonetheless, whether lncRNA prostate cancer-associated transcript 19 (PCAT19) impacts BC development remains unknown.
We performed various bioinformatic analyses, including machine learning models to identify critical regulatory lncRNAs affecting prognosis in BC. The in situ hybridization (ISH) assay was carried out to confirm the expression levels of lncRNA PCAT19 in tissue specimens. MTT assay, wound healing assay, and transwell assay were performed to investigate PCAT19's impact on proliferation, migration, and invasion of BC cells. Mouse xenografts were used to examine the proliferation-inhibiting function of PCAT19 in vivo.
Among the prognosis-associated lncRNAs, PCAT19 predicted a favorable prognosis in BC. Patients with high expression levels of PCAT19 had a lower clinical stage and less lymph node metastasis. The PCAT19-related genes were enriched in signaling pathways involved in tumor development, indicating PCAT19 was an essential regulator of BC. Using the ISH assay, we confirmed the expression level of lncRNA PCAT19 in human BC tissues was lower than normal breast tissues. Moreover, the knockdown of PCAT19 further confirmed its inhibiting ability in BC cell proliferation. Correspondingly, overexpressing PCAT19 reduced tumor size in mouse xenografts.
Our study demonstrated that lncRNA PCAT19 suppressed the development of BC. PCAT19 might be a promising prognostic biomarker, which provides new insights into risk stratification for BC patients.
乳腺癌（BC）是影响女性的最常见恶性肿瘤。探索敏感的生物标志物来诊断和治疗 BC 患者至关重要。最近的研究已经证明，长链非编码 RNA（lncRNA）参与了乳腺癌的进展。然而，lncRNA 前列腺癌相关转录物 19（PCAT19）是否影响 BC 的发展仍不清楚。
我们进行了各种生物信息学分析，包括机器学习模型，以确定影响 BC 预后的关键调节 lncRNA。通过原位杂交（ISH）检测来验证组织标本中 lncRNA PCAT19 的表达水平。MTT 检测、划痕愈合检测和 Transwell 检测用于研究 PCAT19 对 BC 细胞增殖、迁移和侵袭的影响。使用小鼠异种移植模型来检测 PCAT19 在体内对肿瘤增殖的抑制作用。
在预后相关的 lncRNA 中，PCAT19 预测 BC 患者的预后较好。PCAT19 高表达的患者临床分期较低，淋巴结转移较少。PCAT19 相关基因富集在肿瘤发展相关的信号通路中，表明 PCAT19 是 BC 的重要调节因子。通过 ISH 检测，我们证实了 lncRNA PCAT19 在人 BC 组织中的表达水平低于正常乳腺组织。此外，PCAT19 的敲低进一步证实了其对 BC 细胞增殖的抑制作用。相应地，过表达 PCAT19 减少了小鼠异种移植中的肿瘤大小。
我们的研究表明，lncRNA PCAT19 抑制了 BC 的发展。PCAT19 可能是一种有前途的预后生物标志物，为 BC 患者的风险分层提供了新的见解。
