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Circular RNA hsa_circ_0068252 Functions in Cisplatin Resistance and Immune Response via miR-1304-5p/PD-L1 Axis in Non-Small Cell Lung Cancer

Circular RNA hsa_circ_0068252 Functions in Cisplatin Resistance and Immune Response via... Background: Research suggests that circRNAs play important roles in non-small cell lung cancer (NSCLC). The function of hsa_circ_0068252 in NSCLC, especially in cisplatin (DDP) resistance and the mechanisms, was explored in this study. Methods: NSCLC patient samples and two NSCLC cell lines along with corresponding DDP-resistant cell lines were used. Expression levels of circ_0068252 were detected. SiRNA for circ_0068252 and inhibitor for miRNA were used in all functional analyses. A co-culture system of NSCLC cells with CD8+ T cells was used. The cellular location of circ_0068252 was detected and its target miRNA was predicted and verified. Finally, the mechanism responsible for circ_0068252 function on PD-L1 was analyzed using luciferase reporter assay in the two DDP-resistant cell lines, as well as in the co-culture system. The cytotoxicity of T cells was detected by lactate dehydrogenase assay. Results: Our findings revealed that a high level of circ_0068252 was correlated with poor prognosis of NSCLC and DDP resistance. Knockdown of circ_0068252 could promote the sensitivity of DDP-resistant NSCLC cells to DDP. Moreover, knockdown of circ_0068252 could regulate the immune microenvironment which was mediated via CD8+ T cells. Finally, circ_0068252 could up-regulate PD-L1 expression by adsorbing miR-1304-5p. Conclusion: The circ_0068252/miR-1304-5p/PD-L1 signal axis participates in the regulation of DDP resistance and immune escape of NSCLC cells. Our results suggest that circ_0068252 may be a potential diagnostic marker and therapeutic target for DDP-resistant NSCLC. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Chemotherapy Karger

Circular RNA hsa_circ_0068252 Functions in Cisplatin Resistance and Immune Response via miR-1304-5p/PD-L1 Axis in Non-Small Cell Lung Cancer

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References (42)

Publisher
Karger
Copyright
© 2022 S. Karger AG, Basel
ISSN
0009-3157
eISSN
1421-9794
DOI
10.1159/000525231
Publisher site
See Article on Publisher Site

Abstract

Background: Research suggests that circRNAs play important roles in non-small cell lung cancer (NSCLC). The function of hsa_circ_0068252 in NSCLC, especially in cisplatin (DDP) resistance and the mechanisms, was explored in this study. Methods: NSCLC patient samples and two NSCLC cell lines along with corresponding DDP-resistant cell lines were used. Expression levels of circ_0068252 were detected. SiRNA for circ_0068252 and inhibitor for miRNA were used in all functional analyses. A co-culture system of NSCLC cells with CD8+ T cells was used. The cellular location of circ_0068252 was detected and its target miRNA was predicted and verified. Finally, the mechanism responsible for circ_0068252 function on PD-L1 was analyzed using luciferase reporter assay in the two DDP-resistant cell lines, as well as in the co-culture system. The cytotoxicity of T cells was detected by lactate dehydrogenase assay. Results: Our findings revealed that a high level of circ_0068252 was correlated with poor prognosis of NSCLC and DDP resistance. Knockdown of circ_0068252 could promote the sensitivity of DDP-resistant NSCLC cells to DDP. Moreover, knockdown of circ_0068252 could regulate the immune microenvironment which was mediated via CD8+ T cells. Finally, circ_0068252 could up-regulate PD-L1 expression by adsorbing miR-1304-5p. Conclusion: The circ_0068252/miR-1304-5p/PD-L1 signal axis participates in the regulation of DDP resistance and immune escape of NSCLC cells. Our results suggest that circ_0068252 may be a potential diagnostic marker and therapeutic target for DDP-resistant NSCLC.

Journal

Chemotherapy – Karger

Published: Nov 1, 2022

Keywords: Circ_0068252; PD-L1; Cisplatin resistance; CircRNA; Non-small cell lung cancer

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