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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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

In recent years, the problem of cancer resistance has become more and more prominent, seriously affecting treatment efficiency. Circular RNAs (circRNAs) play an important role in cell progression and cancer mechanisms. However, there is a lack of systematic studies on its function in non-small cell lung cancer (NSCLC) resistance. CircPTK2, microRNA-942 (miR-942), and Tripartite motif 16 (TRIM16) levels were detected by Real-time quantitative reverse transcriptase PCR (qRT-PCR). Extracellular acidification rate (ECAR), glucose consumption, and lactate production were assessed using the Seahorse XF96 Glycolysis Analyzer, glucose, and lactate assay kits, respectively. The protein expression was measured with the western bolt Transwell assay was used to determine migration and invasion of transfected cells. (4-5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry were applied to carry out cell proliferation and apoptosis, respectively. The relationship among circPTK2, miR-942, and TRIM16 were determined by using the dual-luciferase reporter assay and RIP assay. circPTK2 (hsa_circ_0008305) and TRIM16 were low expressed, while miR-942 was significantly highly expressed in NSCLC tissues and cell lines. Moreover, overexpression of circPTK2 remarkably inhibited cell growth, metastasis, and glycolysis in A549/CDDP and H1299/CDDP cells. Promotion of miR-942 or inhibition of TRIM16 could reverse the effects of high circPTK2 expression on cell growth, metastasis, and glycolysis in A549/CDDP and H1299/CDDP cells. CircPTK2 overexpression inhibited the growth of A549/CDDP cells in vivo . Furthermore, circPTK2 weakened CDDP resistance of NSCLC through modulating miR-942/TRIM16 axis, providing a novel sight for the treatment of NSCLC and improving the understanding of the CDDP resistance mechanism of NSCLC.