Regulating Oncogenic LncRNA DANCR with Targeted ECO/siRNA Nanoparticles for Non-Small Cell Lung Cancer Therapy

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2022 Jul 11

PMID 35811871

Authors

Calin Nicolescu

Amita Vaidya

Andrew Schilb

Zheng-Rong Lu

Affiliations

Soon will be listed here.

Abstract

Long noncoding RNA (lncRNA) differentiation antagonizing noncoding RNA (DANCR) is a proven oncogenic lncRNA across multiple cancer types. Its effects on cancer cell migration and invasion position it as a potential target for therapy on multiple levels of gene regulation. DANCR is overexpressed in non-small cell lung cancer (NSCLC), the most common lung cancer subtype with poor patient survival. To effectively deliver small interfering RNA (siRNA) against DANCR for NSCLC therapy, we used arginine-glycine-aspartic acid (RGD)-poly(ethylene glycol) (PEG)-(1-aminoethyl)-iminobis[-oleicylcysteinyl-1-aminoethyl)propionamide] (ECO)/small interfering RNA against DANCR (siDANCR) nanoparticles to transfect A549 and NCI-H1299 cells. Over 90% DANCR silencing was observed along with inhibition of cell migration, invasion, and spheroid formation relative to transfection with negative control siRNA in RGD-PEG-ECO nanoparticles. DANCR knockdown further showed efficacy in reducing migration and invasion of epidermal growth factor receptor (EGFR)-inhibitor resistant NSCLC along with resensitization to the inhibitor. RGD-PEG-ECO/siDANCR demonstrated silencing for up to 7 d following a single transfection. The results suggest nanoparticle-mediated RNA interference against DANCR as a potential approach for NSCLC treatment by regulating cell migration and invasion in addition to improving EGFR inhibitor response.

Citing Articles

Comprehensive insights and In silico analysis into the emerging role of LincRNAs in lung diseases pathogenesis; a step toward ncRNA precision.

Hamdy N, Zaki M, Abdelmaksoud N, Elshaer S, Abd-Elmawla M, Rizk N Funct Integr Genomics. 2025; 25(1):34.

PMID: 39912974 PMC: 11802690. DOI: 10.1007/s10142-025-01540-1.

Unraveling the role of long non-coding RNAs in therapeutic resistance in acute myeloid leukemia: New prospects & challenges.

Sharma S Noncoding RNA Res. 2024; 9(4):1203-1221.

PMID: 39036603 PMC: 11259994. DOI: 10.1016/j.ncrna.2024.05.009.

New evidence for a role of DANCR in cancers: a comprehensive review.

Yuan R, Xu Z, Zhang S, Cao X, Dai A, Song L J Transl Med. 2024; 22(1):569.

PMID: 38877534 PMC: 11177382. DOI: 10.1186/s12967-024-05246-z.

Depression of LncRNA DANCR alleviates tubular injury in diabetic nephropathy by regulating KLF5 through sponge miR-214-5p.

Kuang Y, Yang J, Sun M, Rui T, Yang Z, Shi M BMC Nephrol. 2024; 25(1):130.

PMID: 38609873 PMC: 11010359. DOI: 10.1186/s12882-024-03562-6.

Long non-coding RNAs: controversial roles in drug resistance of solid tumors mediated by autophagy.

Saadh M, Almoyad M, Arellano M, Maaliw 3rd R, Castillo-Acobo R, Jalal S Cancer Chemother Pharmacol. 2023; 92(6):439-453.

PMID: 37768333 DOI: 10.1007/s00280-023-04582-z.

References

Chen X, Sievers E, Hou Y, Park R, Tohme M, Bart R . Integrin alpha v beta 3-targeted imaging of lung cancer. Neoplasia. 2005; 7(3):271-9. PMC: 1501139. DOI: 10.1593/neo.04538. View

Chen Y, Li Z, Chen X, Zhang S . Long non-coding RNAs: From disease code to drug role. Acta Pharm Sin B. 2021; 11(2):340-354. PMC: 7893121. DOI: 10.1016/j.apsb.2020.10.001. View

Song Y, Park H, Lee B, Jung J, Lee H, Kim S . Imaging of Integrin αβ Expression in Lung Cancers and Brain Tumors Using Single-Photon Emission Computed Tomography with a Novel Radiotracer Tc-IDA-D-[c(RGDfK)]. Cancer Biother Radiopharm. 2017; 32(8):288-296. PMC: 5661893. DOI: 10.1089/cbr.2017.2233. View

Bai Y, Zhang G, Chu H, Li P, Li J . The positive feedback loop of lncRNA DANCR/miR-138/Sox4 facilitates malignancy in non-small cell lung cancer. Am J Cancer Res. 2019; 9(2):270-284. PMC: 6405976. View

Elayadi A, Samli K, Prudkin L, Liu Y, Bian A, Xie X . A peptide selected by biopanning identifies the integrin alphavbeta6 as a prognostic biomarker for nonsmall cell lung cancer. Cancer Res. 2007; 67(12):5889-95. DOI: 10.1158/0008-5472.CAN-07-0245. View

Yu J, Ju J, Musacchio N, Mathias T, Vitolo M . Long Noncoding RNA DANCR Activates Wnt/β-Catenin Signaling through MiR-216a Inhibition in Non-Small Cell Lung Cancer. Biomolecules. 2020; 10(12). PMC: 7764320. DOI: 10.3390/biom10121646. View

Lu Z, Laney V, Hall R, Ayat N . Environment-Responsive Lipid/siRNA Nanoparticles for Cancer Therapy. Adv Healthc Mater. 2021; 10(5):e2001294. DOI: 10.1002/adhm.202001294. View

Schilb A, Scheidt J, Vaidya A, Sun Z, Sun D, Lee S . Optimization of Synthesis of the Amino Lipid ECO for Effective Delivery of Nucleic Acids. Pharmaceuticals (Basel). 2021; 14(10). PMC: 8537419. DOI: 10.3390/ph14101016. View

Gujrati M, Vaidya A, Mack M, Snyder D, Malamas A, Lu Z . Targeted Dual pH-Sensitive Lipid ECO/siRNA Self-Assembly Nanoparticles Facilitate In Vivo Cytosolic sieIF4E Delivery and Overcome Paclitaxel Resistance in Breast Cancer Therapy. Adv Healthc Mater. 2016; 5(22):2882-2895. PMC: 5589336. DOI: 10.1002/adhm.201600677. View

10.

Frohlich E . The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. Int J Nanomedicine. 2012; 7:5577-91. PMC: 3493258. DOI: 10.2147/IJN.S36111. View

11.

Chen Y, Wu Y, Wang W, Zhang J, Wu Q . Upregulation of lncRNA DANCR functions as an oncogenic role in non-small lung cancer by regulating miR-214-5p/CIZ1 axis. Eur Rev Med Pharmacol Sci. 2020; 24(5):2539-2547. DOI: 10.26355/eurrev_202003_20521. View

12.

Ayat N, Sun Z, Sun D, Yin M, Hall R, Vaidya A . Formulation of Biocompatible Targeted ECO/siRNA Nanoparticles with Long-Term Stability for Clinical Translation of RNAi. Nucleic Acid Ther. 2019; 29(4):195-207. PMC: 6686697. DOI: 10.1089/nat.2019.0784. View

13.

Parvani J, Gujrati M, Mack M, Schiemann W, Lu Z . Silencing β3 Integrin by Targeted ECO/siRNA Nanoparticles Inhibits EMT and Metastasis of Triple-Negative Breast Cancer. Cancer Res. 2015; 75(11):2316-2325. PMC: 4452414. DOI: 10.1158/0008-5472.CAN-14-3485. View

14.

Yan Y, Shi Q, Yuan X, Xue C, Shen S, He Y . DANCR: an emerging therapeutic target for cancer. Am J Transl Res. 2020; 12(7):4031-4042. PMC: 7407722. View

15.

Xu Y, Shang J, Li M, Zhang Y . LncRNA DANCR accelerates the development of multidrug resistance of gastric cancer. Eur Rev Med Pharmacol Sci. 2019; 23(7):2794-2802. DOI: 10.26355/eurrev_201904_17554. View

16.

Islam K, Anggondowati T, Deviany P, Ryan J, Fetrick A, Bagenda D . Patient preferences of chemotherapy treatment options and tolerance of chemotherapy side effects in advanced stage lung cancer. BMC Cancer. 2019; 19(1):835. PMC: 6712837. DOI: 10.1186/s12885-019-6054-x. View

17.

Shibue T, Weinberg R . EMT, CSCs, and drug resistance: the mechanistic link and clinical implications. Nat Rev Clin Oncol. 2017; 14(10):611-629. PMC: 5720366. DOI: 10.1038/nrclinonc.2017.44. View

18.

Charles Richard J, Eichhorn P . Platforms for Investigating LncRNA Functions. SLAS Technol. 2018; 23(6):493-506. PMC: 6249642. DOI: 10.1177/2472630318780639. View

19.

Xiong M, Wu M, Peng D, Huang W, Chen Z, Ke H . LncRNA DANCR represses Doxorubicin-induced apoptosis through stabilizing MALAT1 expression in colorectal cancer cells. Cell Death Dis. 2021; 12(1):24. PMC: 7791116. DOI: 10.1038/s41419-020-03318-8. View

20.

Ma Y, Zhou G, Li M, Hu D, Zhang L, Liu P . Long noncoding RNA DANCR mediates cisplatin resistance in glioma cells via activating AXL/PI3K/Akt/NF-κB signaling pathway. Neurochem Int. 2018; 118:233-241. DOI: 10.1016/j.neuint.2018.03.011. View