Circular RNA circCPA4 promotes tumorigenesis by regulating miR‐214‐3p/TGIF2 in lung cancer

Abstract

Background: Lung cancer is the most prevalent malignancy in adults. Circular RNA (circRNA) circCPA4 (hsa_circ_0082374) is highly expressed in non-small cell lung cancer (NSCLC). The purpose of this study was to explore the role and mechanism of circCPA4 in lung cancer. Methods: CircCPA4, linear CPA4, TGF-β-induced factor homeobox 2 (TGIF2), and microRNA-214-3p (miR-214-3p) levels were measured by real-time quantitative polymerase chain reaction (RT-qPCR). The protein levels of TGIF2, Beclin1, and p62 were assessed by western blot assay. Colony numbers, migration, invasion, apoptosis, and cell cycle progression were examined by colony formation, wound-healing, transwell, and flow cytometry assays, respectively. The binding relationship between miR-214-3p and circCPA4 or TGIF2 was predicted by StarBase or TargetScan and then verified by a dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pulldown assays. The biological role of circCPA4 on lung tumor growth was assessed by a xenograft tumor model in vivo, and TGIF2 and ki-67 expression was assessed by immunohistochemistry. Results: We determined that CircCPA4 and TGIF2 were increased, and miR-214-3p was decreased in lung cancer tissues and cells. Functionally, circCPA4 knockdown could suppress colony formation, migration, invasion, cell cycle progression, and expedite apoptosis of lung cancer cells in vitro. Mechanically, circCPA4 could regulate TGIF2 expression by sponging miR-214-3p. In addition, circCPA4 deficiency inhibited the tumor growth in lung cancer in the mouse model. Conclusions: CircCPA4 could act as a sponge of miR-214-3p to upregulate TGIF2 expression, thereby promoting the progression of lung cancer cells. These findings suggested underlying therapeutic targets for the treatment of lung cancer.

CircCPA4 induces ASCT2 expression to promote tumor property of non‐small cell lung cancer cells in a miR‐145‐5p‐dependent manner

“…Additionally, our data aligned with the reports of high circCPA4 expression in NSCLC tissues and cells 27 . The current study provided evidence that knockdown of circCPA4 impeded the malignant progression of NSCLC cells in vitro, as well as in a mouse tumor model, corroborating existing literature on this topic 13 . The enhancement of glutamine metabolism is known to drive various cancer cell processes, and targeting glutamine metabolism has emerged as a potential therapeutic approach in cancer therapy 28 .…”

“…27 The current study provided evidence that knockdown of circCPA4 impeded the malignant progression of NSCLC cells in vitro, as well as in a mouse tumor model, corroborating existing literature on this topic. 13 The enhancement of glutamine metabolism is known to drive various cancer cell processes, and targeting glutamine metabolism has emerged as a potential therapeutic approach in cancer therapy. 28 In this study, we found that circCPA4 knockdown repressed intracellular glutamine, glutamate and α-KG levels in NSCLC cells.…”

“…12 CircRNA carboxypeptidase A4 (circCPA4, circRNA ID hsa_circ_0082374) has been identified as a promoter of lung cancer progression, but its specific mechanism of action remains unclear. 13 Our study aimed to explore the function and mechanism of circCPA4 in NSCLC.…”

“…In pancreatic cancer, circ‐IARS was upregulated in metastatic tissues and contributed to cancer cell metastasis and shorter survival 12 . CircRNA carboxypeptidase A4 (circCPA4, circRNA ID hsa_circ_0082374) has been identified as a promoter of lung cancer progression, but its specific mechanism of action remains unclear 13 . Our study aimed to explore the function and mechanism of circCPA4 in NSCLC.…”

circCPA4 induces malignant behaviors of prostate cancer via miR-491-5p/SHOC2 feedback loop

“… 7 , 8 circCPA4 has been elucidated to be abundant in cancers and involved in the biological activities of cancer cells. 9 , 10 , 11 However, its biological function in PC remains unclear. miRNAs are crucial in gene expression modification 12 and miRNAs can target specific mRNAs and regulate their expression, while circRNAs can act as a sponge for miRNAs and regulate their availability to targeted mRNAs.…”