hsa_circ_0003222 accelerates stemness and progression of non-small cell lung cancer by sponging miR-527

Abstract

The relationship between circular RNA (circRNA) and cancer stem cells (CSCs) is uncertain. We have investigated the combined influence of CSCs, circRNA (hsa_circ_0003222), and immune checkpoint inhibitors in NSCLC progression and therapy resistance. We constructed lung CSCs (LCSCs; PC9 and A549). The effects of hsa_circ_0003222 in vitro were determined by cell counting, colony and sphere formation, and Transwell assays. A tumor xenograft model of metastasis and orthotopic model were built for in vivo analysis. We found that hsa_circ_0003222 was highly expressed in NSCLC tissues and LCSCs. Higher levels of hsa_circ_0003222 were associated with the stage, metastasis, and survival rate of patients with NSCLC. Reduced levels of hsa_circ_0003222 decreased tumor cell proliferation, migration, invasion, stemness-like properties, and chemoresistance. The silencing of hsa_circ_0003222 was found to downregulate PHF21B expression and its downstream, β-catenin by relieving the sponging effect of miR-527. Moreover, silencing hsa_circ_0003222 alleviated NSCLC resistance to anti-programmed cell death-ligand 1 (PD-L1)-based therapy in vivo. Our data demonstrate the significant role of hsa_circ_0003222 in NSCLC cell stemness-like properties. The manipulation of circRNAs in combination with anti-PD-L1 therapy may alleviate NSCLC stemness and progression.

Inhibition of circular RNA circ_0138959 alleviates pyroptosis of human gingival fibroblasts via the microRNA-527/caspase-5 axis

“…Our data suggested that miR-527 is a target miRNA of circ_0138959 and could be upregulated by inhibition of circ_0138959. miR-527 is a newly discovered tumor suppressor in non-small cell lung cancer (NSCLC), bladder cancer, and glioma [ 45–47 ]. However, there are almost no reports of miR-527 in periodontitis.…”

The Role of Circular RNAs in the Drug Resistance of Cancers

“…Acquired resistance induced by the TME primarily acts as an adaptive response by the host towards pharmacological damage (36). Li et al explored the combined effects of cancer stem cells (CSCs), circRNA (hsa_circ_0003222), and immune checkpoint blockers in NSCLC malignant behavior as well as drug resistance and found that NSCLC resistance to anti-PD-L1-based therapy could be reduced by silencing hsa_circ_0003222 (37). Additionally, circFGFR1 promotes immune evasion of NSCLC cells and enhances tolerance to anti-PD-1-based therapy by interacting with miR-381-3p and upregulating the expression of C-X-C motif chemokine receptor 4 (CXCR4) (38).…”

“…suggested that tumor-derived exosomal circRNA_102481 participated in EGFR-TKI resistance by sponging microRNA-30a-5p to modulate ROR1 in NSCLC ( 82 ). As for immune checkpoint inhibitors, hsa_circ_0003222 and circFGFR1 can promote NSCLC resistance to anti-PD-L1-based and anti-PD-1-based therapies, respectively ( 37 , 38 ). Furthermore, suppression of circIGF2BP3/PKP3 promotes the therapeutic efficacy of anti-PD-1 in a Lewis LADC mouse model ( 39 ).…”

Circular RNA and Its Roles in the Occurrence, Development, Diagnosis of Cancer

“…Many circular RNAs have been discovered to be biomarkers that impact the onset and growth of malignancies in recent years, attracting a lot of attention. They have been identified in lung cancer ( 6 ), hepatocellular carcinoma ( 7 ), gastric cancer ( 8 ), colorectal cancer ( 9 ), and so on. However, the molecular mechanisms and early diagnosis of cancer are not well understood.…”