Ursolic acid (UA), a pentacyclic triterpenoid derived from a variety of medicinal plants, exhibits potent anticancer activity against many types of cancer cells. However, the anticancer mechanism of UA is not clearly understood. Suppression of phosphatase and a tensin homolog deleted on chromosome 10 (PTEN) gene expression leading to activation of the phosphatidylinositol-3-OH kinase (PI3K)/Akt pathway has been observed in many cancers including leukemia, making the PTEN gene and PI3K/Akt pathway a central target for cancer therapy. Here, we demonstrated that UA was able to inhibit growth, induce apoptosis in a human chronic myelogenous leukemia cell line (K562 cells) via upregulation of PTEN gene expression, inhibit Akt kinase activity, change mitochondrial transmembrane potential and reduce the release of cytochrome c and the activity of caspases. These results suggest that UA may elicit its strong antitumor effects via upregulation of the PTEN gene and inhibition of the PI3K/Akt pathway.

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Y-box binding protein-1 (YB-1), a member of Y-box protein family binding DNA and RNA, has been proposed as a novel marker in multiple malignant tumors and found to be associated with tumor malignancy. Neuroblastoma is an embryonal tumor arising from neuroblast cells of the autonomic nervous system, which is the most common cancer diagnosed in infants. It has been reported that YB-1 is highly expressing in various human tumors including nasopharynx, thyroid, lung, breast, colon, ovary, and prostate cancers. This study aimed to investigate the functional role of YB-1 in neuroblastoma by silencing YB-1 using RNA interference (shRNA) in neuroblastoma SH-SY5Y cells. We found that silencing of YB-1 decreased the proliferation, migration, and invasion of SH-SY5Y cells. At molecular level, inhibition of YB-1 decreased the expression level of PCNA as well as MMP-2 in neuroblastoma SH-SY5Y cells. Also, we discovered that YB-1 silencing sensitized SH-SY5Y cells to cisplatin and promoted the apoptosis induced by cisplatin due to down-regulation of multidrug resistance (MDR) 1 protein via NF-κB signaling pathway. Therefore, we consider that targeting YB-1 is promising for neuroblastoma treatment and for overcoming its cisplatin resistance in the development of new neuroblastoma therapeutic strategies.

Multiple myeloma (MM), a malignancy of plasma cells mainly derived from the bone marrow, has remained incurable generally. LncRNA MALAT1 has been reported to be upregulated in the MM cells and knockdown of MALAT1 inhibited MM cell cycle progression and enhanced cell apoptosis. Online target prediction showed that two target sites for MALAT1 existed in miR-188-5p, which has been identified as a tumor suppressor in other types of cancers. However, the role of miR-188-5p in the MM and whether miR-188-5p mediates the MM tumor progression regulated by MALAT1 are still unknown. Herein, four main MM cell lines were adopted to investigate the effects of miR-188-5p on cell proliferation and apoptosis via transfection with miR-188-5p mimic/inhibitor and co-transfection with miR-188-5p inhibitor and MALAT1-shRNA plasmids. Xenograft tumor model was also established to study these effects in vivo. Overexpression of miR-188-5p inhibited cell viability, cell proliferation as well as tumor growth and arrested cell cycle at G1 to S transition, but miR-188-5p knockdown showed opposite effects on the MM cells in vitro and in vivo. Moreover, MALAT1 was shown to be inversely correlated with miR-188-5p expression through direct binding to miR-188-5p, and in turn, miR-188-5p could mediate the MM cell proliferation and apoptosis regulated by MALAT1. These findings indicate that miR-188-5p serves as a tumor suppressor in the progression of the MM and is directly involved in MM cell proliferation and apoptosis regulated by MALAT1, which may provide a potential therapeutic target or prognostic indictor for MM clinical treatment.