lncRNA prostate cancer-associated transcript 18 upregulates activating transcription factor 7 to prevent metastasis of triple-negative breast cancer via sponging miR-103a-3p

Long non-coding RNA (lncRNA) prostate cancer-associated transcript 18 (PCAT18) is a potential diagnostic target for adenocarcinoma. However, its role in triple-negative breast cancer (TNBC) remains largely unknown. Based on data from an online database, a significant decline in lncRNA PCAT18 was observed in patients with TNBC subtype compared to a population with normal breast tissue. Patients with TNBC with high PCAT18 levels presented good outcomes. Patients with TNBC with high PCAT18 had a lower rate of lymph node-positive metastasis than those with low PCAT18. PCAT18-upregulation inhibited, while PCAT18-downregulation promoted, migration and expression of matrix metalloproteinases 9/2 (MMP9/MMP2) and uridylyl phosphate adenosine (uPA) in TNBC cells. Activating transcription factor 7 (ATF7) was positively associated with PCAT18, and ATF7-inhibition abrogated the anti-migration effects of PCAT18 on TNBC cells. Mechanistically, miR-103a-3p directly targeted and inhibited ATF7 expression. PCAT18 competitively sponges miR-103a-3p, promoting the expression of ATF7. Exogenous PCAT18 was associated with lower incidence of lung metastasis followed by the upregulation of ATF7, which was prevented by the treatment of miR-103a-3p mimics. Collectively, PCAT18 was expressed at low levels in TNBC, and PCAT18 could sponge miR-103a-3p and promote ATF7 expression, resulting in prevention of TNBC metastasis. Thus, PCAT18 can serve as a predictive factor for patients with metastatic TNBC.

长链非编码RNA（long non-coding RNA，lncRNA）前列腺癌相关转录本18（prostate cancer-associated transcript 18，PCAT18）是一种潜在的腺癌诊断靶点。然而，其在三阴性乳腺癌（triple-negative breast cancer，TNBC）中的作用仍未被充分阐明。基于在线数据库的数据，与正常乳腺组织人群相比，三阴性乳腺癌亚型患者的PCAT18表达水平显著降低。PCAT18高表达的三阴性乳腺癌患者预后较好，且其淋巴结阳性转移率低于PCAT18低表达患者。在三阴性乳腺癌细胞中，PCAT18表达上调可抑制细胞迁移及基质金属蛋白酶9/2（matrix metalloproteinases 9/2，MMP9/MMP2）与腺苷尿苷磷酸（uridylyl phosphate adenosine，uPA）的表达，而PCAT18表达下调则可促进上述过程。激活转录因子7（activating transcription factor 7，ATF7）与PCAT18呈正相关，且抑制ATF7可消除PCAT18对三阴性乳腺癌细胞的抗迁移作用。机制研究显示，miR-103a-3p可直接靶向并抑制ATF7的表达；PCAT18可通过竞争性海绵吸附miR-103a-3p，促进ATF7的表达。外源性PCAT18过表达可降低肺转移发生率，且该效应伴随ATF7表达上调，而miR-103a-3p模拟物处理可阻断这一过程。综上，PCAT18在三阴性乳腺癌中呈低表达状态，其可通过竞争性海绵吸附miR-103a-3p促进ATF7表达，从而抑制三阴性乳腺癌的转移。因此，PCAT18可作为转移性三阴性乳腺癌患者的预测因子。