Our data suggest that hMSC contribute to quiescence and therapy resistance of persistent AML cells.

Relapse of acute myeloid leukemia (AML) has a very poor prognosis and remains a common cause of treatment failure in patients with this disease. AML relapse is partially driven by the chemoresistant nature of leukemia stem cells (LSCs), which remains poorly understood, and our study aimed at elucidating the underlying mechanism. Accumulating evidences show that long noncoding RNAs (lncRNAs) play a crucial role in AML development. Herein, the lncRNA, LINC00152, was identified to be highly expressed in CD34+ LSCs and found to regulate the self-renewal of LSCs derived from AML patients. Importantly, LINC00152 upregulation was correlated with the expression of 16 genes within a 17-gene LSC biomarker panel, which contributed to the accurate prediction of initial therapy resistance in AML. Knockdown of LINC00152 markedly increased the drug sensitivity of leukemia cells. Furthermore, LINC00152 expression was found to be correlated with poly (ADP-ribose) polymerase 1 (PARP1) expression in AML, whereas LINC00152 knockdown significantly decreased the expression of PARP1. Upregulation of LINC00152 or PARP1 was associated with poor prognosis in AML patients. Collectively, these data highlight the importance and contribution of LINC00152 in the regulation of self-renewal and chemoresistance of LSCs in AML.

Pancreatic cancer is a common cause of worldwide cancer-related mortality with a poor 5-year survival rate. Aldehyde dehydrogenase (ALDH) activity is a possible marker for malignant stem cells in solid organ systems, including the pancreas, and N,N-diethylaminobenzaldehyde (DEAB) is able to inhibit ALDH activity. In the present study, the role of DEAB in the treatment of pancreatic cancer cells and the potential underlying mechanisms were investigated. The ALDH activities of pancreatic cancer cell lines treated with or without DEAB were analyzed by an ALDEFLUOR™ assay. The Cell Counting Kit-8 and colony formation assays, and cell cycle analysis were used to evaluate the viability, colony-forming ability and cell quiescence of cell lines under DEAB treatment, respectively. DEAB and/or gemcitabine-induced cell apoptosis was assessed by flow cytometry. DEAB reduced ALDH activity and inhibited the proliferation, colony-forming ability and cell quiescence of pancreatic cancer cell lines. Compared with respective controls, DEAB alone and the combination of gemcitabine and DEAB significantly decreased cell viability and increased cell apoptosis. Moreover, reverse transcription-PCR and western blotting were used to measure the expressions of B cell lymphoma 2 (Bcl2) associated X protein (Bax) and Bcl2 mRNA and protein. The anti-cancer effect of DEAB was associated with upregulation of Bax expression. Therefore, targeting ALDH with DEAB may be a potential therapeutic choice for pancreatic cancer, demonstrating a synergic effect with gemcitabine.

Background: As the most common female malignancy, the incidence and mortality of endometrial carcinoma (EC) continue to increase worldwide. The effects of traditional standard therapy are limited; thus, novel therapeutic strategies urgently need to be developed. We sought to provide prospective targeting insights into EC therapeutics by comprehensively examining and confirming the biological molecular characterization of EC genes.Methods: The molecular characterization of EC genes was integrated and analyzed using data fromThe Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Project (GTEx) databases. The differentially expressed genes (DEGs) were identified, and the abnormal expression of some core cell-cycle proteins in the EC specimens was determined by examining and integrating the TCGA and GTEx data. The enriched signaling pathways involved in tumor progression were also examined.Results: Immunohistochemical staining data from the Human Protein Atlas database showed that the differential expression levels of the cyclin dependent kinase inhibitor 2A (CDKN2A) and tyrosine threonine kinase (TTK) molecules, and the high messenger ribonucleic acid (RNA) levels of CDKN2A and TTK were associated with a poor prognosis in EC patients. High TTK expression was also significantly correlated with the tumor progression associated signaling pathways, such as the cell-cycle, nucleolus, and RNA processing pathways. The inhibition of TTK expression by a TTK inhibitor (NTRC0066-0) significantly suppressed the proliferation of the EC cells and synergistically increased the sensitivity of the EN and AN3-CA EC cell lines. Conclusions:The findings suggest that the TTK inhibitor could be used in EC therapy. This study highlighted the potential predictive role of TTK molecules and showed that TTK molecules might serve as prospective targets for EC therapy.