Mixed‐lineage kinase 3 (MLK3), the mitogen‐activated protein kinase kinase kinase (MAP3K), has been recognized as a player in tumorigenesis and oncogenic signalling, yet its detailed functions and signalling in cervical cancer have not been fully elucidated. Here, we identify that cervical cancer cells display higher mRNA and protein levels of MLK3 than normal cervical epithelial squamous cells. In HeLa and SiHa cell, MLK3 knockdown using siRNA remarkably suppressed cell survival and promoted cell apoptosis, with increased expression of the apoptosis‐related protein Bax and reduced Bcl‐2. Moreover, MLK3 knockdown promoted cell autophagy, demonstrated by increased ratio of autophagy‐related proteins LC3II/LC3I and decreased p62 expression in MLK3 depletion cells. Furthermore, MLK3 knockdown remarkably abolished Notch‐1 expression in cervical cancer cells. By co‐treating Hela cells with MLK3 specific siRNA and pcDNA3.1‐Notch‐1 overexpression plasmid or autophagy inhibitor 3‐MA, we found that MLK3 played its role in cervical cancer cells via the Notch‐1/autophagy network. Our results demonstrate the importance of MLK3 in cervical cancer progression via modulating the Notch‐1/autophagy network, and suggest that MLK3 is a promising therapeutic target for cervical cancer.

This study aims to identify differentially expressed proteins related with platinum sensitivity and to find biomarkers for predicting platinum response and survival outcomes in patients with high-grade serous ovarian cancer (HGSOC). Eligible HGSOC patients were divided into platinum-sensitive and platinum-resistant groups according to platinum-free interval (PFI). Tissue protein lysates from tumor tissues were subjected to an in-solution tryptic digest followed by tandem mass tag (TMT) labeling of the resulting peptides and mass spectrometric analysis. Candidate proteins were identified using differentially expressed protein and gene set enrichment analysis (GSEA) and confirmed by immunohistochemistry (IHC), and their survival relevance was evaluated in The Cancer Genome Atlas (TCGA) ovarian cancer cohort. The results showed that there was a significant difference in the protein expression profiling between the two patient groups. In the GSEA model, a gene set of 239 extracellular matrix (ECM)-related proteins was significantly enriched in the platinum-sensitive group [normalized enrichment score (NES) = 3.82, q < 10−5], and this finding was confirmed in TCGA ovarian cancer cohort. Interestingly, an ECM-related gene expression, serpin family A member 10 (SERPINA10), was identified to be significantly positively correlated with overall survival (OS) and progression-free survival (PFS) in TCGA ovarian cancer cohort (all p < 0.05). IHC results demonstrated that HGSOC patients with high SERPINA10 expression had longer PFI than the patients with low SERPINA10 expression (9 vs. 5 months, p = 0.038), and the SERPINA10 expression had an area under the receiver operating characteristic curve (AUC) value of 0.758 (95% CI = 0.612–0.905; p = 0.005) to discriminate the platinum-sensitive group from the platinum-resistant group. In conclusion, the results suggested that SERPINA10 could be a promising biomarker for predicting the response and survival in platinum-based chemotherapy of HGSOC.

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Purpose: Long noncoding RNAs (lncRNAs) and glycolysis regulate multiple types of cancer. However, the prognostic roles and biological functions of glycolysis-related lncRNAs in lung adenocarcinoma (LUAD) remain unclear. In this study, we investigated the role of glycolysis-related lncRNAs in LUAD. Patients and Methods: We retrieved glycolysis-related genes from the Molecular Signatures Database and screened for prognostic glycolysis-related lncRNAs from The Cancer Genome Atlas. Results: We identified three LUAD subtypes (clusters 1-3) by univariate Cox regression analysis and consensus clustering. Patients in cluster 1 had the best overall survival rates. Immune, stromal, and cytolytic-activity scores were the highest in cluster 1. The expression of immune checkpoint molecules (programmed cell death protein 1 and cytotoxic T-lymphocyteassociated protein 4) and other immune-related indicators was the highest in cluster 1, whereas that of epithelial cell biomarkers (Cadherin 1, Cadherin 2, and MET) was the lowest. Therefore, patients in cluster 1 may benefit from immunotherapy. Lasso-Cox regression and multivariate Cox regression analyses were used to select nine lncRNAs to build a robust prognostic model of LUAD. The area under the curve classifier values and a nomogram performed well in predicting survival times for patients with LUAD. The expression levels of nine lncRNAs were validated by quantitative reverse transcriptase-polymerase chain reaction analysis, and most of these lncRNAs were significantly related to immune-related mRNAs. Gene set enrichment analysis revealed that the high-risk group was enriched for cell cycle-related pathways and the low-risk group was enriched for pathways associated with immunity or immune-related diseases. Conclusion:The LUAD subtypes and prognostic model developed here may help in clinical risk stratification, prognosis management, and treatment decisions for patients with LUAD.