MiR-1307-5p targeting TRAF3 upregulates the MAPK/NF-κB pathway and promotes lung adenocarcinoma proliferation

Abstract

Background Non-small cell lung cancer (NSCLC) includes lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). MicroRNA (miRNA) plays an important role in the regulation of post-transcriptional gene expression in animals and plants, especially in lung adenocarcinoma. Methods MiR-1307-5p is an miRNA with significant differences screened by the second generation of high-throughput sequencing in the early stage of our research group. In the current study, a series of in vitro and in vivo experiments were carried out. MiR-1307-5p mimic, miR-1307-5p inhibitor, and NC were transfected into A549 and H1299 lung adenocarcinoma cells. The correlation between miR-1307-5p and clinicopathological features in pathological samples was analyzed using a lung adenocarcinoma tissue microarray, and miR-1307-5p expression was detected by qPCR. CCK-8, EdU, colony formation, scratch test, and Transwell assays were used to observe cell proliferation and migration. Double luciferase assay, western blot, qPCR, and immunohistochemistry were employed in confirming the target relationship between miR-1307-5p and TRAF3. Western blotting was used to analyze the relationship between miR-1307-5p and the NF-κB/MAPK pathway. Finally, the effect of miR-1307-5p on tumor growth was studied using a subcutaneous tumorigenesis model in nude mice. Results Increased miR-1307-5p expression was significantly related to decreased overall survival rate of lung adenocarcinoma patients, revealing miR-1307-5p as a potential oncogene in lung adenocarcinoma. MiR-1307-5p mimic significantly promoted while miR-1307-5p inhibitor reduced the growth and proliferation of A549 and H1299 cells. MiR-1307-5p overexpression significantly enhanced the migration ability while miR-1307-5p inhibition reduced the migration ability of A549 and H1299 cells. Target binding of miR-1307-5p to TRAF3 was confirmed by double luciferase assay, western blot, qPCR, and immunohistochemistry. miR-1307-5p caused degradation of TRAF3 mRNA and protein. MiR-1307-5p targeted TRAF3 and activated the NF-κB/MAPK pathway. TRAF3 colocalized with p65 and the localization of TRAF3 and p65 changed in each treatment group. Tumor volume of the lv-miR-1307-5p group was significantly larger than that of the lv-NC group, and that of the lv-miR-1307-5p-inhibitor group was significantly smaller than that of the lv-NC group. Conclusion In conclusion, miR-1307-5p targets TRAF3 and activates the NF-κB/MAPK pathway to promote proliferation in lung adenocarcinoma.

Nuclear export protein CSE1L interacts with P65 and promotes NSCLC growth via NF-κB/MAPK pathway

“… 37 P65 played a key role in the regulation of MAPK signal pathway. 39 , 40 It was reported that ERK was localized in the cytoplasm of resting cells, and extracellular stimulation inclined to induce a rapid and robust nuclear translocation of ERK. 41 In our study, CSE1L activated ERK phosphorylation by effecting the protein expression of P65, then regulated the cell cycle and promoted NSCLC cell proliferation.…”

A microRNA Signature of Metastatic Colorectal Cancer

“…Mir-155_5p, which was preferentially expressed in mLu and PM, is reported to be specifically expressed in lymphocytes and macrophages 22 , possibly indicating higher abundance of these cell types in the metastases compared to pCRC. Less is known about the biological activity of Mir-1307_5p, although reports have suggested a role in lung adenocarcinoma proliferation 47 and as a predictor of hepatocellular carcinoma metastasis 48 . The identification of this miRNA as highly expressed in mCRC points to its involvement in metastasis, and Mir-1307_5p therefore represents another target for further studies.…”

Nuclear Export Protein CSE1L Interacts with P65 and Promotes NSCLC Growth via NF-κB/MAPK Pathway

“…We know that there are two distinct NF-κB signaling pathways: 1) the classical pathway, primarily activated by pathogens and in ammatory mediators, and 2) the alternative pathway, which involves the NF-κB-inducing kinase (NIK, also known as MAP3K14) [37]. P65 plays a key role in the regulation of MAPK signal pathway [39,40]. It was reported that while ERK was localized in the cytoplasm of resting cells, many of its substrates are (Fig.…”