Circ‐SNAP47 (hsa_circ_0016760) and miR‐625‐5p are regulators of WEE1 in regulation of chemoresistance, growth and invasion of DDP‐tolerant NSCLC cells via ceRNA pathway

Abstract

Circular RNA‐synaptosome associated protein 47 (circ‐SNAP47; Hsa_circ_0016760) is oncogenic in non‐small‐cell lung cancer (NSCLC); however, its role is undescribed in cis‐diamminedichloroplatinum II (DDP) resistance. We attempted to investigate its expression, role and mechanism in DDP‐tolerant NSCLC. As a result, circ‐SNAP47 expression was upregulated in human DDP‐tolerant NSCLC tissues and cells, accompanied with WEE1 G2 checkpoint kinase (WEE1) upregulation and microRNA (miR)‐625‐5p downregulation. Functionally, interfering circ‐SNAP47 and/or restoring miR‐625‐5p curbed the 50% inhibitory concentration of DDP, colony formation, cell proliferation and invasion, accompanied with apoptotic rate promotion and depressions of multidrug resistance (MDR) markers MDR1 and MRP1, anti‐apoptosis protein Bcl‐2, and pro‐invasion protein MMP9. Notably, circ‐SNAP47 interference suppressed xenograft tumor growth of DDP‐tolerant NSCLC cells by elevating miR‐625‐5p and descending WEE1. Mechanistically, circ‐SNAP47 directly targeted miR‐625‐5p, and miR‐625‐5p further targeted WEE1. Therefore, circ‐SNAP47‐miR‐625‐5p‐WEE1 axis might participate in chemoresistance and progression of DDP‐tolerant NSCLC.

Circ_0001402 knockdown suppresses the chemoresistance and development of DDP‐resistant cutaneous squamous cell carcinoma cells by functioning as a ceRNA for miR‐625‐5p

“…MiR-625-5p has established a crucial role in repressing cancer development and chemoressitance. 15,18,24 Furthermore, miR-625-5p could be sponged by several circRNAs, including circ_0016760. 18 In the current research, miR-625-5p inhibition was discovered to reverse the functions of circ_0001402 KPNA4, the sole transporter for NF-κB and an activator of NF-κB signalling, 25,26 promoted cell proliferation, invasion, tumour microenvironment, metastasis and paclitaxel-resistant characteristics in gastric, lung and endometrial cancers.…”

“…15,18,24 Furthermore, miR-625-5p could be sponged by several circRNAs, including circ_0016760. 18 In the current research, miR-625-5p inhibition was discovered to reverse the functions of circ_0001402 KPNA4, the sole transporter for NF-κB and an activator of NF-κB signalling, 25,26 promoted cell proliferation, invasion, tumour microenvironment, metastasis and paclitaxel-resistant characteristics in gastric, lung and endometrial cancers. [26][27][28] Besides, KPNA4 was required for the prevention of epidermal differentiation and Ras/ ERK signalling activation in the head and neck of squamous cell carcinoma.…”

“…Subsequently, miR‐625‐5p was testified as a target miRNA for circ_0001402. MiR‐625‐5p has established a crucial role in repressing cancer development and chemoressitance 15,18,24 . Furthermore, miR‐625‐5p could be sponged by several circRNAs, including circ_0016760 18 .…”

“…MiR‐625‐5p is a key regulator in human cancers through functioning as a tumour suppressor 15–17 . Moreover, elevated expression of miR‐625‐5p sensitizes DDP‐resistant non‐small‐cell lung cancer cells to DDP by regulating WEE1 18 . Nevertheless, the role of miR‐625‐5p in the DDP resistance of CSCC remains undefined.…”

“…[15][16][17] Moreover, elevated expression of miR-625-5p sensitizes DDP-resistant non-small-cell lung cancer cells to DDP by regulating WEE1. 18 Nevertheless, the role of miR-625-5p in the DDP resistance of CSCC remains undefined. Besides, karyopherin subunit alpha 4 (KPNA4) is a newly identified gene relevant to cancer biology, malignant development and DDP resistance in squamous cell carcinomas, including CSCC.…”