A novel cancer-germline gene DAZL promotes progression and cisplatin resistance of non-small cell lung cancer by upregulating JAK2 and MCM8.

Germline-specific genes are usually activated in cancer cells and drive cancer progression; such genes are called cancer-germline or cancer-testis genes. The RNA-binding protein DAZL is predominantly expressed in germ cells and plays a role in gametogenesis as a translational activator or repressor. However, its expression and role in non-small cell lung cancer (NSCLC) are unknown. Here, mining of RNA-sequencing data from public resources and immunohistochemical analysis of tissue microarrays showed that DAZL was expressed exclusively in testis among normal human tissues but ectopically expressed in NSCLC tissues. Testis and NSCLC cells expressed the shorter and longer transcript variants of the DAZL gene, respectively. Overexpression of the longer DAZL transcript promoted tumor growth in a mouse xenograft model. Silencing of DAZL suppressed cell proliferation, colony formation, migration, invasion, and cisplatin resistance in vitro and tumor growth in vivo. Quantitative proteomic analysis based on tandem mass tag and Western blot analysis showed that DAZL upregulated the expression of JAK2 and MCM8. RNA-binding protein immunoprecipitation assays showed that DAZL bound to the mRNA of JAK2 and MCM8. The JAK2 inhibitor fedratinib attenuated the oncogenic outcomes induced by DAZL overexpression, whereas silencing MCM8 counteracted the effects of DAZL overexpression on cisplatin-damaged DNA synthesis and half-maximal inhibitory concentration of cisplatin. In conclusion, DAZL was identified as a novel cancer-germline gene that enhances the translation of JAK2 and MCM8 to promote NSCLC progression and resistance to cisplatin, respectively. These findings suggest that DAZL is a potential therapeutic target in NSCLC.

ChIP-chip data for identifying target genes and consensus binding sequences of mutant p53 in MDA-MB-468 breast cancer cells.

The tumor suppressor p53 exerts its role mainly as a transcription factor. The TP53 gene, which encodes the p53 protein, is the most commonly mutated gene in human cancers, particularly triple negative breast cancer (TNBC). Variations in the TP53 gene occur mainly in exons 5-8 and result in missense mutations in the DNA-binding domain of the p53 protein that alter DNA binding specificity. To identify the target genes of mutant p53, we performed chromatin immunoprecipitation followed by DNA microarray (ChIP-chip). Briefly, the TNBC cell line MDA-MB-468 containing the endogenous p53-R273H mutation (the arginine residue at position 273 is mutated to a histidine) was cross-linked with 1% formaldehyde and ultrasonically sheared to generate chromatin fragments in a range of 200∼1000 bp. An aliquot of the sheared chromatin was kept as input, and the other chromatin was precipitated with a p53 monoclonal antibody. DNA was purified from the precipitated chromatin and the unprecipitated chromatin (i.e., input), amplified, and labeled with Cy5 (ChIP DNA) or Cy3 (input DNA). Cy5- and Cy3-labeled DNA samples were cohybridized with the NimbleGen Human ChIP-chip 2.1 M Deluxe Promoter Array. The raw and analyzed data are described in this article. They are useful for identifying target genes and consensus binding motifs of the p53 R273H mutant and for further clarifying the molecular mechanism underlying the oncogenic activity of the p53 mutant.

Datasets for the effects of RUNX2 silencing on transcriptomic and metabolomic profiles in SJSA-1 osteosarcoma cells.

Osteosarcoma is the most common primary malignant bone tumor with a high risk of metastasis and recurrence. Metabolic reprogramming is a hallmark of osteosarcoma and other cancers and is associated with genetic and epigenetic alterations. RUNX2 is an important transcription factor for osteoblastic differentiation, and aberrant expression of the gene contributes to the development and progression of osteosarcoma. To identify the effects of RUNX2 silencing on transcriptomic and metabolomic profiles in osteosarcomas, we generated SJSA-1 osteosarcoma cells stably expressing RUNX2 shRNA and SJSA-1 cells stably expressing scramble shRNA and analyzed transcriptome and metabolome profiles in the two cell types using Illumina NovaSeq 6000 and ultrahigh-performance liquid chromatography coupled with time-of-flight mass spectrometry, respectively. The datasets can be used by researchers to identify novel targets of RUNX2 and elucidate the role and underlying mechanism of RUNX2 in osteosarcoma pathogenesis and metabolic reprogramming.