Nan Lin

Systematic Identification of Genomic Markers for Guiding Iron Oxide Nanoparticles in Cervical Cancer Based on Translational Bioinformatics

Magnetic iron oxide nanoparticle (MNP) drug delivery system is a novel promising therapeutic option for cancer treatment. Material issues such as fabrication and functionalized modification have been investigated; however, pharmacologic mechanisms of bare MNPs inside cancer cells remain obscure. This study aimed to explore a systems pharmacology approach to understand the reaction of the whole cell to MNPs and suggest drug selection in MNP delivery systems to exert synergetic or additive anti-cancer effects. HeLa and SiHa cell lines were used to estimate the properties of bare MNPs in cervical cancer through 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) and enzyme activity assays and cellular fluorescence imaging. A systems pharmacology approach was utilized by combining bioinformatics data mining with clinical data analysis and without a predefined hypothesis. Key genes of the MNP onco-pharmacologic mechanism in cervical cancer were identified and further validated through transcriptome analysis with quantitative reverse transcription PCR (qRT-PCR). Low cytotoxic activity and cell internalization of MNP in HeLa and SiHa cells were observed. Lysosomal function was found to be impaired after MNP treatment. Protein tyrosine kinase 2 beta (PTK2B), liprin-alpha-4 (PPFIA4), mothers against decapentaplegic homolog 7 (SMAD7), and interleukin (IL) 1B were identified as key genes relevant for MNP pharmacology, clinical features, somatic mutation, and immune infiltration. The four key genes also exhibited significant correlations with the lysosome gene set. The qRT-PCR results showed significant alterations in the expression of the four key genes after MNP treatment in HeLa and SiHa cells. Our research suggests that treatment of bare MNPs in HeLa and SiHa cells induced significant expression changes in PTK2B, PPFIA4, SMAD7, and IL1B, which play crucial roles in cervical cancer development and progression. Interactions of the key genes with specific anti-cancer drugs must be considered in the rational design of MNP drug delivery systems.

BUB1B Promotes Ovarian Cancer Cell Proliferation and Metastasis by Activating the Wnt/β‐Catenin Pathway

ABSTRACT Background BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) has been found to participate in cancer progression. Nevertheless, the function and mechanism of BUB1B in ovarian cancer (OC) remain unknown. Method Based on datasets GSE14407, GSE18520, and the TCGA combined GTEx database, the differently expressed genes (DEGs) between OC tissues and para‐carcinoma tissues were identified. These DEGs were subjected to protein–protein interaction analysis to obtain hub genes, with BUB1B serving as a candidate for further study. Subsequently, the prognostic value was analyzed. To elucidate the role of BUB1B, knockdown experiments were conducted in vitro and in vivo to assess alterations in malignant behaviors, while β ‐catenin expression was quantified by qRT‐PCR and western blot. Moreover, the Wnt/ β ‐catenin pathway inhibitor LGK974 was utilized to demonstrate whether the effects of BUB1B are mediated by the Wnt/ β ‐catenin pathway. Results High BUB1B expression was observed in OC tissues and cell lines, and it was identified as a hub DEG with prognostic value in OC. Following BUB1B knockdown, cell proliferation, migration, invasion, and tumor growth and metastasis were suppressed in vitro and in vivo. Mechanically, BUB1B knockdown inhibited the expression of β ‐catenin and inactivated the Wnt/ β ‐catenin pathway. In addition, BUB1B overexpression promoted the malignant behavior of OC cells, which was inhibited by LGK974. Conclusion BUB1B is an oncogene whose expression level is negatively correlated with the prognosis of OC patients. Mechanically, BUB1B promotes the progression of OC via the Wnt/ β ‐catenin pathway. Our study offers a potential therapeutic target for OC treatment.