MiR-199a-5p Targets DUSP14 to Regulate Cell Proliferation, Invasion and Stemness in Non-small Cell Lung Cancer

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 Apr 22

PMID 38644862

Authors

Ying Zheng

Chaokun Yang

Shaoqiang Xie

Desheng Liu

Hui Wang

Jinxin Liu

Affiliations

Soon will be listed here.

Abstract

Background: Non-small cell lung cancer (NSCLC) shows the highest morbidity among malignant tumors worldwide. Despite improvements of diagnosis and treatment, patient prognosis remains unfavorable. Therefore, there is a need to discover a novel treatment strategy for NSCLC. DUSP14 is related to various cancers as the regulatory factor for cellular processes. However, its specific roles in NSCLC and the upstream modulator remain largely unclear.

Methods: DUSP14 expression patterns within the lung cancer patient cohort from TCGA database were analyzed using UALCAN online tool. Different databases including miRDB, starbase, and Targetscan were employed to screen the upstream regulator of DUSP14. DUSP14 and miR-199a-5p expression was determined by qRT-PCR and Western blot techniques. To confirm binding interaction of DUSP14 with miR-199a-5p, we conducted a dual-luciferase reporter assay. Cell viability, migration, and stemness properties were assessed using CCK-8, EdU (5-ethynyl-2'-deoxyuridine) incorporation, transwell invasion, and sphere formation assays. The effect of DUSP14 silencing on tumorigenesis was assessed with the NSCLC cell xenograft mouse model.

Results: Our study discovered that DUSP14 exhibited high expression within NSCLC tumor samples, which is related to the dismal prognostic outcome in NSCLC patients. Silencing DUSP14 impaired NSCLC cell proliferation, migration, and tumor sphere formation. Besides, we identified miR-199a-5p as the upstream regulatory factor for DUSP14, and its expression was negatively related to DUSP14 level within NSCLC tissues. Introducing miR-199a-5p recapitulated the function of DUSP14 silencing in NSCLC cell aggressiveness and stemness. Moreover, knocking down DUSP14 efficiently inhibited tumor formation in NSCLC cells of the xenograft model.

Conclusions: Our study suggests that DUSP14 is negatively regulated by miR-199a-5p within NSCLC, whose overexpression is required for sustaining NSCLC cell proliferation, invasion and stemness.

References

Chen M, Chuang H, Yeh Y, Chou C, Tan T . Dual-specificity phosphatases 22-deficient T cells contribute to the pathogenesis of ankylosing spondylitis. BMC Med. 2023; 21(1):46. PMC: 9921195. DOI: 10.1186/s12916-023-02745-6. View

Yang C, Chiu L, Tan T . TRAF2-mediated Lys63-linked ubiquitination of DUSP14/MKP6 is essential for its phosphatase activity. Cell Signal. 2015; 28(1):145-51. DOI: 10.1016/j.cellsig.2015.10.017. View

Kielbowski K, Ptaszynski K, Wojcik J, Wojtys M . The role of selected non-coding RNAs in the biology of non-small cell lung cancer. Adv Med Sci. 2023; 68(1):121-137. DOI: 10.1016/j.advms.2023.02.004. View

Jimenez T, Barrios A, Tucker A, Collazo J, Arias N, Fazel S . DUSP9-mediated reduction of pERK1/2 supports cancer stem cell-like traits and promotes triple negative breast cancer. Am J Cancer Res. 2020; 10(10):3487-3506. PMC: 7642669. View

Treiber T, Treiber N, Meister G . Publisher Correction: Regulation of microRNA biogenesis and its crosstalk with other cellular pathways. Nat Rev Mol Cell Biol. 2019; 20(5):321. DOI: 10.1038/s41580-019-0106-6. View

Romano G, Le P, Nigita G, Saviana M, Micalo L, Lovat F . A-to-I edited miR-411-5p targets MET and promotes TKI response in NSCLC-resistant cells. Oncogene. 2023; 42(19):1597-1606. PMC: 10336698. DOI: 10.1038/s41388-023-02673-y. View

Zhang R, Meng Z, Wu X, Zhang M, Piao Z, Jin T . PD-L1/p-STAT3 promotes the progression of NSCLC cells by regulating TAM polarization. J Cell Mol Med. 2022; 26(23):5872-5886. PMC: 9716221. DOI: 10.1111/jcmm.17610. View

Kia V, Paryan M, Mortazavi Y, Biglari A, Mohammadi-Yeganeh S . Evaluation of exosomal miR-9 and miR-155 targeting PTEN and DUSP14 in highly metastatic breast cancer and their effect on low metastatic cells. J Cell Biochem. 2018; 120(4):5666-5676. DOI: 10.1002/jcb.27850. View

Sanders B, Yamamoto T, McMellen A, Woodruff E, Berning A, Post M . Targeting DUSP Activity as a Treatment for High-Grade Serous Ovarian Carcinoma. Mol Cancer Ther. 2022; 21(8):1285-1295. PMC: 9357222. DOI: 10.1158/1535-7163.MCT-21-0682. View

10.

Yang X, Zheng Y, Tan J, Tian R, Shen P, Cai W . MiR-199a-5p-HIF-1α-STAT3 Positive Feedback Loop Contributes to the Progression of Non-Small Cell Lung Cancer. Front Cell Dev Biol. 2021; 8:620615. PMC: 7929999. DOI: 10.3389/fcell.2020.620615. View

11.

Han H, Li Y, Qin W, Wang L, Yin H, Su B . miR-199b-3p contributes to acquired resistance to cetuximab in colorectal cancer by targeting CRIM1 via Wnt/β-catenin signaling. Cancer Cell Int. 2022; 22(1):42. PMC: 8796585. DOI: 10.1186/s12935-022-02460-x. View

12.

Guo Y, He Y . Comprehensive analysis of the expression of SLC30A family genes and prognosis in human gastric cancer. Sci Rep. 2020; 10(1):18352. PMC: 7591519. DOI: 10.1038/s41598-020-75012-w. View

13.

Singh M, Altameemi S, Lares M, Newton M, Setaluri V . Role of dual specificity phosphatases (DUSPs) in melanoma cellular plasticity and drug resistance. Sci Rep. 2022; 12(1):14395. PMC: 9399232. DOI: 10.1038/s41598-022-18578-x. View

14.

Marie-Claire C, Benturquia N, Lundqvist A, Courtin C, Noble F . Characteristics of dual specificity phosphatases mRNA regulation by 3,4-methylenedioxymethamphetamine acute treatment in mice striatum. Brain Res. 2008; 1239:42-8. DOI: 10.1016/j.brainres.2008.08.050. View

15.

Cuttano R, Afanga M, Bianchi F . MicroRNAs and Drug Resistance in Non-Small Cell Lung Cancer: Where Are We Now and Where Are We Going. Cancers (Basel). 2022; 14(23). PMC: 9740066. DOI: 10.3390/cancers14235731. View

16.

Harrandah A, Mora R, Chan E . Emerging microRNAs in cancer diagnosis, progression, and immune surveillance. Cancer Lett. 2018; 438:126-132. DOI: 10.1016/j.canlet.2018.09.019. View

17.

Hua Q, Jin M, Mi B, Xu F, Li T, Zhao L . LINC01123, a c-Myc-activated long non-coding RNA, promotes proliferation and aerobic glycolysis of non-small cell lung cancer through miR-199a-5p/c-Myc axis. J Hematol Oncol. 2019; 12(1):91. PMC: 6728969. DOI: 10.1186/s13045-019-0773-y. View

18.

Rosolen D, Nunes-Souza E, Marchi R, Tofolo M, Antunes V, Berti F . MiRNAs Action and Impact on Mitochondria Function, Metabolic Reprogramming and Chemoresistance of Cancer Cells: A Systematic Review. Biomedicines. 2023; 11(3). PMC: 10045760. DOI: 10.3390/biomedicines11030693. View

19.

Park J, Wollmann G, Urbiola C, Fogli B, Florio T, Geley S . Sprouty2 enhances the tumorigenic potential of glioblastoma cells. Neuro Oncol. 2018; 20(8):1044-1054. PMC: 6280149. DOI: 10.1093/neuonc/noy028. View

20.

Shi Y, Li K, Xu K, Liu Q . MiR-155-5p accelerates cerebral ischemia-reperfusion injury via targeting DUSP14 by regulating NF-κB and MAPKs signaling pathways. Eur Rev Med Pharmacol Sci. 2020; 24(3):1408-1419. DOI: 10.26355/eurrev_202002_20198. View