Circulating hsa_circ_0072309, acting via the miR-100/ACKR3 pathway, maybe a potential biomarker for the diagnosis, prognosis, and treatment of brain metastasis from non-small-cell lung cancer.

Background: One of the main causes of lung cancer-related death is brain metastasis (BM). Finding early indicators of BM derived from lung cancer is crucial. Therefore, this study was designed to determine if serum hsa_circ_0072309 may be employed as a potential biomarker for BM induced by non-small-cell lung cancer (NSCLC) and to understand its possible underlying mechanism.

Methods: Primary lung cancer and healthy neighboring tissues were obtained from all patients, while BM tissues were taken from BM+ patients. Serum specimens were collected from all patients and healthy volunteers. Hsa_circ_001653, miR-100, and ACKR3 RNA expressions were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and atypical chemokine receptor 3 (ACKR3) protein expression by western blotting (WB), immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA). In order to examine the effect of serum hsa_circ_0072309 and its relevant mechanism on BM development, an NSCLC-associated BM model in mice was established.

Results: According to the results, miR-100 expression was down-regulated in primary lung cancer tissues compared to healthy lung tissues in all NSCLC patients, and circ_0072309 and ACKR3 expression were up-regulated. In BM tissues compared with primary lung tumors of BM+ patients, in serum samples from all patients compared to healthy volunteers, and in lung tumors of BM+ patients compared to those from BM- patients. Patients' serum exhibits the same level of hsa_circ_0072309/miR-100/ACKR3 expression as in BM samples. Advanced tumor-node-metastasis (TNM) stage, higher BM, shorter post-operative overall survival (OS), and progression-free survival (PFS) are all substantially associated with increased serum circ_0072309 levels in BM+ patients. In animal models, serum owning hsa_circ_0072309 from BM+ patients facilitates BM formation by regulating the miR-100/ACKR3 pathway.

Conclusions: The current preliminary research reveals serum hsa_circ_0072309 as a possible biomarker and target for early diagnosis, prognosis, and therapy of NSCLC-derived BM and suggests a substantial role for the hsa_circ_0072309/miR-100/ACKR3 axis in the formation of BM from NSCLC.