Circ_0010235 facilitates lung cancer development and immune escape by regulating miR‐636/PDL1 axis

Abstract

Background: Circular RNAs (circRNAs) are a class of important regulators in various human cancers, including lung cancer. Here, we aimed to investigate the role of circ_0010235 in lung cancer. Methods: The expression of circ_0010235, microRNA-636 (miR-636) and PDL1 was measured by quantitative real-time PCR (qRT-PCR). Cell proliferation was evaluated by CCK-8, colony formation, and 5-ethynyl-2 0 -deoxyuridine (EdU) assays. Cell apoptosis was detected by flow cytometry. Cell invasion was assessed by transwell assay. All protein levels were determined by western blot assay. In order to detect the roles of circ_0010235 in immune escape, lung cancer cells were cocultured with peripheral blood mononuclear cells (PBMCs) or cytokine-induced killer (CIK) cells in vitro. The relationship between miR-636 and circ_0010235 or PDL1 was verified by dual-luciferase reporter assay and RNA pulldown assay. Immunohistochemistry (IHC) analysis was used to detect Ki67 and programmed death-ligand 1 (PDL1) expression. A xenograft tumor model was established to verify the function of circ_0010235 in vivo. Results: Circ_0010235 was overexpressed in lung cancer. Circ_0010235 knockdown inhibited proliferation, invasion and immune escape and promoted apoptosis of lung cancer cells. MiR-636 was a target of circ_0010235, and miR-636 inhibition reversed the effects of circ_0010235 knockdown in lung cancer cells. PDL1 was a direct target of miR-636, and miR-636 suppressed the proliferation and invasion and increased apoptosis and antitumor immunity in lung cancer cells by downregulating PDL1. Moreover, circ_0010235 positively regulated PDL1 expression by sponging miR-636. Additionally, circ_0010235 knockdown hampered tumorigenesis in vivo. Conclusion: Circ_0010235 knockdown inhibited lung cancer progression and increased antitumor immunity by regulating the miR-636/PDL1 axis.

Identification of Novel miRNAs, Targeting Genes, Signaling Pathway, and the Small Molecule for Overcoming Oxaliplatin Resistance of Metastatic Colorectal Cancer

“…Another example is bta-miR-26a which also reduced the abundance of PCK1 [44,45]. Moreover, the oncosuppressor miR-20a-3p was identified in melanoma, tongue squamous cell carcinoma, and hepatocellular carcinoma, and the oncosuppressor miR-636 was also identified in lung cancer, nasopharyngeal carcinoma, cervical cancer, endometrial cancer, ovarian cancer, and hepatocellular carcinoma [46][47][48][49][50][51][52][53][54][55][56]. It was reported that high miR-20a-3p and miR-636 expression were correlated with poor OS of CRC patients and this was consistent with our results.…”

Synergistic Immunoregulation: harnessing CircRNAs and PiRNAs to Amplify PD-1/PD-L1 Inhibition Therapy

“…Additionally, circ_0010235 knockdown can further hamper the development of NSCLC. 104 More importantly, circ_0010235 has been found to increase the expression of PD-L1 via the miR-636/PD-L1 axis. 104 Thus, such candidate can potentially provide multiple anti-cancer effects in cancer treatment.…”

circPTP4A2 knockdown suppresses NSCLC progression via regulating proliferation and activating anti-tumor immunity

“…The development of NSCLC involves many molecular abnormalities and is accompanied by complex biological processes [ 8 ]. The expression of non-coding RNAs is a useful indicator to describe the molecular characteristics of NSCLC and plays a crucial role in the regulation of the immune system [ 9 , 10 ]. Many circRNAs function as oncogenic or inhibitory non-coding RNAs that participate in tumor progression and tumor immunity of NSCLC, such as circC190 and circNDUFB2 [ 11 , 12 ].…”