Hsa_circ_0000520 Promotes Invasion and Metastasis of Breast Cancer Cells by Targeting HSP90AA1.

Abstract

Background: Breast cancer (BC) ranks among the predominant malignancies in females globally. Growing research indicates that circular RNAs (circRNAs) exert important regulatory functions in multiple cancers. Nevertheless, the biological functions and underlying molecular mechanisms of numerous circRNAs in BC remain largely unelucidated.

Methods: Firstly, based on existing database and our previous research, hsa_circ_0000520 has been found to be closely associated with BC and has potential for clinical application. Then, its circular nature was confirmed. The expression in BC cells and tumor tissues was explored by quantitative real-time polymerase chain reaction (qRT-PCR). The biological effects on BC cell growth, invasion and metastasis were verified by vitro experiments. To clarify the molecular mechanism, Chromatin Isolation by RNA Purification (ChIRP) assay coupled with mass spectrometry (MS), RNA immunoprecipitation (RIP), and Western blotting were used to identify and validate interacting proteins. Rescue experiments were conducted using the HSP90AA1 inhibitor tanespimycin. Associations between hsa_circ_0000520 expression and clinicopathological characteristics were analyzed.

Results: Hsa_circ_0000520 was confirmed to be a stable circular RNA predominantly localized in the cytoplasm. Functionally, it served as an oncogene in BC and enhanced the capacities of BC cells to invade and metastasize. Mechanistically, heat shock protein 90 alpha (also termed HSP90AA1) was identified as a key interacting parter of it. Inhibition of HSP90AA1 abrogated the pro-metastatic effects of hsa_circ_0000520 but did not affect its pro-proliferative role, indicating a specific cooperation in driving invasion and metastasis. Clinically, it was significantly increased in BC cells, tumor tissues, and serum samples. Importantly, its elevated expression correlates with advanced clinical stage, specific molecular subtypes, and poor prognosis in BC patients.

Conclusion: Our research results revealed an unrecognized regulatory axis, in which hsa_circ_0000520 facilitates BC cells progression by coordinating with HSP90AA1, highlighting hsa_circ_0000520 could be a promising diagnostic indicator and potential treatment target for BC.