BackgroundMakorin RING zinc finger-2 (MKRN2) belongs to the makorin RING zinc finger family and is a novel ubiquitin E3 ligase targeting the p65 subunit of NF-κB to negatively regulate inflammatory responses; however, the relationship between MKRN2 and tumorigenesis remains unclear. In this study, we clarified the role of MKRN2 in non-small cell lung cancer (NSCLC).MethodsTumor specimens collected from 261 NSCLC patients from 2013 to 2017 were retrieved from the Pathology Archive of the First Affiliated Hospital of China Medical University, and we performed assays to evaluate MKRN2 expression and to determine the impact of MKRN2 silencing and overexpression on NSCLC-cell migration and invasion.ResultsWe demonstrated that MKRN2 expression was associated with lymph node metastasis, p-TNM stage, cancer-cell differentiation, and poor prognosis. By altering the expression of MKRN2 in selected cell lines, we found that MKRN2 inhibited cell migration and invasion through downregulation of the PI3K/Akt pathway.ConclusionsThese results suggested that MKRN2 inhibited NSCLC progression by reducing the metastatic potential of cancer cells. Our findings provide critical insight into the association of MKRN2 expression with favorable clinicopathological characteristics in NSCLC patients and suggested that MKRN2 plays a role in inhibiting NSCLC development.

Background Studies have shown that E3 ubiquitin ligase CBLL1 plays multiple roles in development and tumorigenesis. CBLL1 is over‐expressed in colon cancer and associated with cancer cell proliferation. While, the overexpression of CBLL1 inhibited the estrogenic dependent cell proliferation and migration in ER alpha dependent breast cancer cell MCF‐7. Methods We used an immunohistochemical method to detect CBLL1 expression in human NSCLC and corresponding normal lung tissues and analyzed its relationship with clinicopathological parameters. Moreover, we investigated the role of CBLL1 in NSCLC cell behavior by inhibiting its expression in A549 and H1299 cells. Results In this study, we found that CBLL1 was frequently upregulated in non‐small lung cancer (NSCLC) tissues compared to the adjacent nontumor tissues. We found that the high expression of CBLL1 was associated with the tumor size in NSCLC tissues. It has been recently reported that CBLL1 promotes cell proliferation and invasion in A549 and H460 cells. Our results confirmed that CBLL1 promoted the proliferation by promoting G1/S cell cycle transition in NSCLCs cells. Moreover, CBLL1 knockdown inhibited cell invasion via increased E‐cadherin protein expression, and decreased expression of MMP2 and MMP9 in NSCLC cell lines. The protein expression of E‐cadherin was increased after CBLL1 depletion while the E‐cadherin mRNA was not affected after knockdown of the endogenous CBLL1. Conclusion These results provide important insights for using CBLL1 as an oncogenic marker gene in the development and progression of non‐small cell lung cancer.

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Tripartite motif-containing 67 (TRIM67), an E3 ubiquitin ligase, belongs to the TRIM protein family. The relationship between TRIM67 and tumorigenesis is not fully clear. Here, we elucidated TRIM67 function in non-small cell lung cancer (NSCLC). TRIM67 immunostaining results were correlated with clinicopathological features. Moreover, the function of TRIM67 in cultured NSCLC cells was evaluated by MTT, colony formation, and Transwell assays. TRIM67 expression was associated with tumor size, lymph node metastasis, p-TNM stage, cancer cell differentiation, and poor prognosis. We altered TRIM67 expression in A549 and H1299 cell lines, and the results showed that TRIM67 promoted cell proliferation, migration, invasion and EMT by positively regulating the Notch pathway. Collectively, the results showed that TRIM67 promotes NSCLC progression through the Notch pathway and that TRIM67 expression is associated with clinicopathological features, indicating that TRIM67 may play an important role in promoting the development of NSCLC and could be applied as not only an important prognostic biomarker but also a therapeutic target in NSCLC.

In a meta-analysis, the long noncoding RNA cancer susceptibility candidate 8 (CASC8) was found to be a cancer susceptibility gene closely related to lung cancer, but its functions in lung cancer are unknown. In the Cancer Genome Atlas database, the expression of CASC8 was significantly higher in non-small cell lung cancer than in adjacent normal tissues, and high expression of CASC8 was associated with poor prognosis in patients with lung adenocarcinoma. Silencing CASC8 inhibited proliferation, migration, and invasion in non-small cell lung cancer cell lines. Silencing CASC8 also promoted sensitivity to osimertinib through Forkhead box M1 (FOXM1). Therefore, this pathway can be exploited in patients with lung cancer resistant to targeted therapies. Our study revealed for the first time that silencing CASC8 inhibited the proliferation, migration, and invasion of non-small cell lung cancer cells and promoted their sensitivity to osimertinib, suggesting that CASC8 is closely related to the occurrence and development of non-small cell lung cancer. This may provide insight into mechanisms of treatment for non-small cell lung cancer.