N-mytistoyltransferase 1 and 2 are potential tumor suppressors and novel targets of miR-182 in human non-small cell lung carcinomas

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2022-09, Vol.171, p.70-81
• Main Authors: Zhang, Tong, Goel, Arul, Xu, Xin, Wu, Yazhou, Tang, Erjiang, Zhang, Fanping, Li, Yuan, Li, Hanhua, Cai, Yuchan, Weng, Wenhao
• Format: Article
• Language: English
• Subjects: miR-182; N-myristoyltransferases; NSCLC; Prognosis; Tumor suppressor
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2022.07.021

•Highlighting important role of N-myristoyltransferases in non-small cell lung carcinogenesis.•Showed that NMT1 and NMT2 act as tumor-suppressors in NSCLC.•Discovered that NMT1 is able to interact with NMT2 through their initial 10aa, and promotes NMT2 expression by enhancing its stability.•Unravel a novel mechanism that oncogenic miR-182 regulates both NMT1 and NMT2, and controls N-myristoylation level in NSCLC. Non-small cell lung cancer (NSCLC) accounts for about 80% of lung cancer diagnoses across the world. Despite recent appreciable improvements in treatment plans for patients with NSCLC, the prognosis for those with the cancer still remains poor. Recently, a growing number of studies have shown that N-myristoyltransferases (NMTs) may be critical in carcinogenesis, however, the functional and clinical significance of this pathway in NSCLC remains unclear and requires further research. Initially, we evaluated the expression levels of NMT1 or NMT2 in a clinical cohort comprising of 303 paired primary NSCLC tissues and matched normal mucosae by using ELISA. We subsequently performed a tissue microarray analysis (TMA) to confirm its expression pattern in an independent validation cohort (n = 78). Then, we used a publicly available KM plotter database (n = 1921) to evaluate the prognostic impact of NMT1 and NMT2 in NSCLC. Lastly, a series of in-vitro molecular/cellular and animal experiments were performed for mechanistic understanding of the role of N-myristoyltransferases in NSCLC. Our ELISA data revealed that the expression level of NMT1 and NMT2 was down-regulated in tumor tissues (n = 303, P