Clinical ReportsLncRNA PCAT6 activated by SP1 facilitates the progression of breast cancer by the miR-326/LRRC8E axisZhu, Qiannana; Wang, Shuia,*; Shi, YuenianbAuthor Information aDepartment of Breast Disease, The First Affiliated Hospital of Nanjing Medical University bDepartment of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website, www.anti-cancerdrugs.com. *Shui Wang is the co-corresponding author. Correspondence to Yuenian Shi, MD, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China, Tel: +86 516 728 5351; fax: +718 962 6675; e-mail: [email protected] Anti-Cancer Drugs: February 2022 - Volume 33 - Issue 2 - p 178-190 doi: 10.1097/CAD.0000000000001253 Buy SDC Metrics Abstract Breast cancer is an aggressive malignancy with high morbidity in females worldwide. Extensive studies reveal that long noncoding RNAs (lncRNAs) are abnormally expressed and act as key regulators in various cancers, including breast cancer. In this work, we investigated the role and regulatory mechanism of lncRNA prostate cancer-associated transcript 6 (PCAT6) in breast cancer progression. Our findings revealed that PCAT6 was overexpressed in breast cancer tissues and cell lines. Furthermore, elevation of PCAT6 reflected an adverse prognosis of patients. Functional experiments indicated that PCAT6 knockdown hampered cell proliferation, facilitated apoptosis and cell cycle arrest in vitro, and inhibited tumor growth in vivo. We also found that the transcription factor SP1 could bind to the PCAT6 promoter and promoted its expression. Subsequently, it was verified that PCAT6 was a molecular sponge for microRNA-326 (miR-326), and the leucine-rich repeat containing the eight family member E (LRRC8E) was a direct target of miR-326. Rescue assays revealed that LRRC8E overexpression attenuated the suppressive effect of PCAT6 knockdown on cellular progression of breast cancer. In summary, this study demonstrated that SP1-activated PCAT6 promoted the malignant behaviors of breast cancer cells by regulating the miR-326/LRRC8E axis. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.