PCAT6 Regulates IGF2BP1/PD-L1 to Promote Immune Escape in Breast Cancer

Sep 22, 2026

This open-access research article investigates how prostate cancer-associated transcript 6 (PCAT6) drives immune escape in triple-negative breast cancer (TNBC). Analysis of 68 paired TNBC specimens and lentivirus-manipulated TNBC cell lines shows PCAT6 is upregulated and associated with advanced stage and lymph node metastasis. PCAT6 knockdown reduces proliferation, migration, invasion, and PD-L1 expression, while increasing CD8+ T cell cytotoxicity and IFN-γ production. Mechanistically, PCAT6 interacts with IGF2BP1 to stabilize PD-L1 mRNA.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Objective

Methods

Results

Conclusion

Introduction

The Journal of Gene Medicine RESEARCH ARTICLE OPEN ACCESS PCAT6 Regulates IGF2BP1/PD-L1 to Promote Immune Escape in Breast Cancer Dingping Sun1 | Shanglong Sun2 | Jing Li1 | Liping Gu3 | Weijian Yang1 | Li Shang4 1Department of Surgical Oncology, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, Gansu, China | 2Department of Breast Surgery, Xigu District Maternal and Child Health Care Hospital, Lanzhou, Gansu, China | 3Department of Pathology, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, Gansu, China | 4Department of Breast Surgery, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, Gansu, China Correspondence: Li Shang ([shanggli1@126.com](shanggli1@126.com)) Received: 12 January 2026 | Revised: 14 July 2026 | Accepted: 1 August 2026 Keywords: IGF2BP1 | long noncoding RNA | PCAT6 | PD-L1 | triple-negative breast cancer ABSTRACT Objective: This study aims to elucidate the mechanism through which prostate cancer-associated transcript 6 (PCAT6) modulates immune escape in triple-negative breast cancer (TNBC), focusing on its interaction with IGF2BP1 and PD-L1 . Methods: We analyzed 68 paired TNBC clinical specimens and utilized TNBC cells (BT-549, MDA-MB-468) with lentivirusmediated gene manipulation. Functional assays included cell counting kit-8, EdU incorporation, Transwell migration/invasion, and co-culture with activated CD8+ T cells. Immune function was assessed through LDH release, ELISA (IFN-γ and granzyme B), and flow cytometry. Molecular interactions were investigated via RNA immunoprecipitation, RNA pulldown, fluorescence in situ hybridization, and actinomycin D-based mRNA stability assays. Results: PCAT6 was markedly upregulated in TNBC tissues and cell lines, correlating with advanced tumor stage and lymph node metastasis. PCAT6 knockdown restrained tumor cell proliferation, migration, and invasion while downregulating PD-L1 expression. In co-culture systems, PCAT6 depletion enhanced CD8+ T cell cytotoxicity, evidenced by increased inflammatory factor secretion and elevated IFN-γ+ CD8+ T cell proportion. Mechanistically, PCAT6 interacted with IGF2BP1 in the cytoplasm and promoted IGF2BP1-mediated stabilization of PD-L1 mRNA. Rescue experiments confirmed that PCAT6 required IGF2BP1 to sustain PD-L1 expression and mRNA stability. Conclusion: PCAT6 facilitates TNBC immune escape by enhancing PD-L1 mRNA stability through IGF2BP1, identifying the PCAT6/IGF2BP1/PD-L1 axis as a potential therapeutic target for breast cancer immunotherapy. 1 | Introduction Triple-negative breast cancer (TNBC) stands one of the most aggressive BC subtypes with the poorest prognosis [1] . Defined by the lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, TNBC is limited to targeted therapeutic options and often develops resistance to conventional radiotherapy and chemotherapy [2, 3]. Consequently, the 5-year survival rate for TNBC is significantly lower than that of other subtypes [4] . Recently, immune checkpoint inhibitors (ICIs) targeting the programmed deathligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) axis have offered new hope for TNBC patients [5] . However, only approximately 20%–30% of patients benefit from this approach, with tumor immune escape mechanisms representing a major limitation to treatment efficacy [6] . Long noncoding RNAs (lncRNAs) are transcripts exceeding 200 nucleotides in length that do not encode proteins [7] . They exert diverse effects in tumor progression, metastasis, This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2026 The Author(s) . The Journal of Gene Medicine published by John Wiley & Sons Ltd. The Journal of Gene

FAQs

What is the main objective of this study on TNBC?

The study aims to clarify the mechanism by which PCAT6 modulates immune escape in triple-negative breast cancer, focusing on PCAT6’s interaction with IGF2BP1 and PD-L1.

How was immune escape assessed in the experiments?

Immune function was measured using LDH release, ELISA for IFN-γ and granzyme B, and flow cytometry, including co-culture with activated CD8+ T cells.

What mechanistic pathway did the authors find connecting PCAT6, IGF2BP1, and PD-L1?

PCAT6 interacts with IGF2BP1 in the cytoplasm and promotes IGF2BP1-mediated stabilization of PD-L1 mRNA. Rescue experiments indicate PCAT6 requires IGF2BP1 to sustain PD-L1 expression and mRNA stability.

Sep 22, 2026

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