Colorectal cancer (CRC) is the third most commonly diagnosed cancer and common cause of cancer‑related deaths. Radiotherapy has become a routine treatment for CRC. However, radioresistance affects therapeutic efficacy. Long non‑coding RNA urothelial carcinoma associated 1 (UCA1) has been demonstrated to be overexpressed in several tumors and predicts a poor prognosis. In the present study, we revealed that lncRNA‑UCA1 was overexpressed in colorectal cancer tissue and colon cancer cells when compared to normal tissue and cells. Quantitative real‑time PCR revealed that the expression of UCA1 was significantly higher in CRC tissues after chemoradiotherapy. Downregulation of UCA1 enhanced the radiosensitivity of CCL244 cells via inhibition of the colony formation, proliferation and promotion of radiation‑induced apoptosis and G2/M arrest. Moreover, downregulation of UCA1 suppressed the epithelial‑mesenchymal transition (EMT) in CCL244 cells.

Mounting evidence has been shown that integrin-mediated cellular adhesion confers resistance to chemotherapy of multiple myeloma. The molecular mechanism underlying cell adhesion-mediated drug resistance (CAM-DR) is, however, poorly understood. In this report, we demonstrated that RPMI 8,226 cells accumulated p27(Kip1) in the nucleus when they were adhered to fibronectin (FN). The adhesion-mediated p27(Kip1) nuclear recruitment was regulated via the down-regulation of Jab1, a negative regulator of cell cycle. Overexpression of Jab1 reversed the elevated p27(Kip1) in the nucleus, which needed phosphorylation of p27(Kip1) on Serine 10, whereas inhibition of Jab1 by siRNA further increased the elevated p27(Kip1). Furthermore, we found overexpression of Jab1 did not affect 8,226 cells adhesion to FN, but reversed doxorubicin or mitoxantrone-induced CAM-DR phenotype. In conclusion, our data suggest that Jab1 plays an important role in CAM-DR, which depends on pSer10-p27(Kip1)-mediated subcellular localization of p27(Kip1). The understanding of this novel molecular mechanism may prove valuable in designing new therapeutic approaches for CAM-DR in Multiple myeloma.

Abstract. Decoy receptor 3 (DcR3) is abundantly expressed in human tumors and protects cells from a wide range of apoptotic stimuli. In this study, we demonstrate that DcR3 is overexpressed in pancreatic carcinoma cells, and that the pancreatic carcinoma cell lines, Panc-1 and SW1990, are resistant to Fas ligand (FasL)-mediated apoptosis. To further define the function of DcR3 in cell growth and apoptosis, we used small interfering RNA (siRNA) to knockdown the expression of the DcR3 gene in Panc-1 and SW1990 cells. Our results revealed that the silencing of DcR3 expression enhanced the inhibitory effects of FasL and reduced the capabiltiy of the cells for proliferation and colony formation in vitro. In addition, the downregulation of DcR3 modulated the cell apoptotic regulators, Fas-associated death domain (FADD), caspase-3 and caspase-8, thus triggering cell apoptosis. Furthermore, the knockdown of DcR3 inhibited the growth of Panc-1 tumor xenografts. Taken together, our findings indicate that DcR3 is important in cancer progression and may be a used as a potential therapeutic target for the gene therapy of pancreatic carcinoma.

Abstract. Chemotherapy is one of the commonly used strategies in gastric cancer, especially for unresectable patients, but it becomes insensitive to repeated administration of even the most effective chemotherapeutic agents, such as cisplatin. Given this, there is an urgent need for developing chemosensitizers to overcome acquired resistance to chemotherapeutic agents. Interleukin-24 (IL-24), a cytokine-tumor suppressor, shows broad-spectrum and tumor-specific antitumor properties, and studies have demonstrated that IL-24 could conspicuously restore the chemosensitivity of MDR cancer cells. Herein, we developed a human MDR gastric cancer cell subline, SGC7901/ CDDP, by repeated selection of resistant clones of parental sensitive cells, and further investigated the chemosensitizing effects and the underlying mechanisms of adenovirus-medi- IntroductionGastric cancer is the fourth leading cause of cancer-related death in the world (1). To date, chemotherapy is the most frequently used fundamental treatment for gastric cancer. However, the main barrier to successful chemotherapy is MDR caused by insensitivity to multiple chemotherapeutic agents after exposure to a single chemotherapeutic drug (2). For decades, the most representative consensus is the overexpression of drug efflux pumps (such as P-gp) occupying a critical position in development of MDR. Consequently, several innovative chemosensitizers against P-gp, such as verapamil, trifluoperazine and cyclosporine, have been found to enhance chemosensitivity of MDR phenotype cancer cells (3). However, the clinical application of these chemosensitizers showed disappointing results (4,5), indicating that there are some unknown molecules and mechanisms also responsible for MDR. Recent studies have verified that some novel factors including defective apoptosis pathway, enhanced DNA repair activity, or altered metabolism of drugs play a critical role in promoting formation of MDR (6). Though the underlying mechanisms have been deeply studied in vitro and in vivo (6-9), the precise mechanisms involved in MDR have not been Abbreviations: MDR, multidrug resistance; P-gp, P-glycoprotein;RT-PCR, reverse transcriptase polymerase chain reaction; IC 50 , 50% inhibitory concentration

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