Background: Endometrial cancer is one of the most common malignancies of the female genital tract. Although the overall five-year survival of EC is much higher than other genital tumor, 25% of the total patients with high risk to develop more aggressive diseases. The metastasis in EC patients is the main cause of death. The MEK inhibitor, which has significant effect on malignant molenoma, lung cancer and so on, has bright future in EC. Method: Here we treated the EC cell line HEC50 and HEC1A with different concentration of RG7420. The CCK8 was used to detecte the cell proliferation rate. Microarray analyzed the difference of LncRNAs in EC cells with or without RG7420. Luciferase reporter assay and RNA immunoprecipitation assay(RIP) were performed to verified the regulation among MALAT1, miR-129-5p and TGF-β-activated kinase 1 (TAK1). QRT-PCR and WB were used to detect the changes in mRNA and protein levels. We also performed ISH to detect the MALAT level in EC paraffin section. Results: We found the RG7420 significantly inhibited the viability and mobility of EC cell lines. Then we analyzed the profile of LncRNA in HEC50 with or without RG7420. We found after treated with IC50 of HEC50, the metastasis-associated lung adenocarcinoma transcript-1(MALAT1) decreased 6.13 times with up-regulation of tumor suppressor miR-129-5p. Our data also provided that MALAT1 may work as endogenous sponge for miR-129-5p. Here we predicted and proved TGF-β-activated kinase 1 (TAK1), encoded by MAP3K7, is the target of miR-129-5p and works as the key factor in metastasis of EC. Meanwhile we compared the MALAT1 level in EC paraffin section by in-situ hybridization. Rerospective analysis assessed the corelation between the MALAT1 level and the clinical characters of EC, MALAT1 is a poor prognostic marker of EC. Furthermore we over-expressed MALAT1 in EC cells, the function of RG7420 was reversed. Conclusion: Taken together, our data uncovered RG7420 inhibited the proliferation and migration of EC cell through MALAT1/miR-129-5p/TAK1 pathway. MALAT1 is a poor prognostic marker of EC.

Rationale: Immune checkpoint inhibitors (ICIs) have been widely used in the treatment of various types of cancers worldwide, which is the most significant breakthrough in cancer therapy in recent years. Despite their excellent benefits in anti-tumor efficacy, a subset of patients will experience various autoimmune toxicities, termed as immune-related adverse events (irAEs), which can affect almost any organ systems, but related to the pulmonary and pancreatic islets simultaneously has rarely been reported and discussed. Patient concerns: In this report, we describe a rare case of a 65-year-old man patient with advanced small cell lung cancer (SCLC) who suffered general fatigue, dry cough, chest tightness, shortness of breath and polyuria-polydipsia syndrome after the eighth cycle treatment with programmed cell death ligand-1 (PD-L1) inhibitor durvalumab. Diagnoses: According to the results of laboratory tests, chest computed tomography and multidisciplinary discussion, the patient was eventually diagnosed with ICI-related pneumonitis and autoimmune diabetes mellitus. Interventions: Multiple daily subcutaneous insulin injections, empirical anti-infection and immunosuppression treatment with corticosteroids were performed. Outcomes: After the cessation of durvalumab and comprehensive treatment, the patient’s respiratory condition was relieved significantly and his blood glucose was well controlled with insulin therapy. Lessons: With the widespread use of ICIs, there will be more patients developing these rare but severe irAEs in clinical practice, which should attract great attention of both clinicians and patients.