CRISPR interference and activation of the microRNA-3662-HBP1 axis control progression of triple-negative breast cancer.

Abstract

MicroRNA-3662 (miR-3662) is minimally expressed in normal human tissues but is highly expressed in all types of cancers, including breast cancer. As determined with The Cancer Genome Atlas dataset, miR-3662 expression is higher in triple-negative breast cancers (TNBCs) and African American breast cancers than in other breast cancer types. However, the functional role of miR-3662 remains a topic of debate. Here, we found that inhibition or knockout of endogenous, mature miR-3662 in TNBC cells suppresses proliferation and migration in vitro and tumor growth and metastasis in vivo. Functional analysis revealed that, for TNBC cells, knockout of miR-3662 reduces the activation of Wnt/β-catenin signaling. Furthermore, using CRISPR-mediated miR-3662 activation and repression, dual-luciferase assays, and miRNA/mRNA immunoprecipitation assays, we established that HMG-box transcription factor 1 (HBP-1), a Wnt/β-catenin signaling inhibitor, is a target of miR-3662 and is most likely responsible for miR-3662-mediated TNBC cell proliferation. Our results suggest that miR-3662 has an oncogenic function in tumor progression and metastasis via an miR-3662-HBP1 axis, regulating the Wnt /β-catenin signaling pathway in TNBC cells. Since miR-3662 expression occurs a tumor-specific manner, it is a promising biomarker and therapeutic target for patients who have TNBCs with dysregulation of miR-3662, especially African Americans.

• Authors: Baozhu Yi, Shuaibin Wang, Xinran Wang, Zhichao Liu, Chao Zhang, Ming Li, Song Gao, Shi Wei, Sejong Bae, Erica Stringer-Reasor, Lizhong Wang, Runhua Liu
• Journal: Oncogene (Oncogene) Vol. 41 Issue 2 Pg. 268-279 (01 2022) ISSN: 1476-5594 [Electronic] England
• PMID: 34728806 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Nature Limited.

Topics

• Animals
• Cell Line, Tumor
• Cell Proliferation
• Clustered Regularly Interspaced Short Palindromic Repeats (genetics)
• Disease Progression
• Female
• Humans
• Mice
• Transfection
• Triple Negative Breast Neoplasms (genetics)
• Wnt Signaling Pathway (genetics)