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Abstract. Human telomerase reverse transcriptase (hTERT) is the key component of telomerase catalytic activity, and is associated with tumorigenesis. Recent evidence suggests that the down-regulation of hTERT could rapidly induce an antiproliferative effect in tumor cells, independent of the telomereelongating function of the enzyme. To test the immediate antitumor efficacy of this down-regulation, antisense oligodeoxynucleotides (AS-ODN) targeting hTERT mRNA were transfected into two human pancreatic cancer cell lines in vitro. In both cell lines, single transfection with AS-ODN decreased the level of hTERT mRNA expression in a dosedependent manner (from 0.05 to 0.2 μM), while transfection with 0.2 μM hTERT AS-ODN for 24 h achieved the maximum down-regulation of hTERT mRNA. Additionally, 0.2 μM AS-ODN significantly reduced telomerase activity in the cell lines. However, after the first transfection with 0.2 μM AS-ODN, almost no inhibition of cell proliferation was observed in either of the lines, while multiple consecutive transfections with the same concentration of AS-ODN resulted in a continuous reduction in cell viability, the significant inhibition of colony formation ability and increased cell apoptotic rates. Cell cycle analysis indicated that hTERT AS-ODN mainly arrested the cell cycle at the G0/G1 phase in the cells. The data validate an antisense oligonucleotide approach to hTERT inhibition therapy in pancreatic cancer cells. IntroductionPancreatic cancer is one of the most common causes of cancerrelated mortality in the world, and the incidence of the disease has been steadily increasing. Surgery is the only viable treatment option; however, the cancer is usually diagnosed at a late stage, making tumor resection possible in less than 20% of patients (1,2). Less than 5% of all patients diagnosed with pancreatic cancer can expect to survive over 5 years (2,3). Although a great deal of attention has been directed towards the therapeutic treatment of pancreatic cancer, including various adjuvant, neo-adjuvant, locoregional or radio-chemotherapy strategies, the prognosis for patients has not improved significantly, and developing new therapeutic strategies for the treatment of the disease is a top priority.Telomerase is a ribonucleoprotein enzyme responsible for adding telomeric repeats to the 3' ends of chromosomes. The activation of telomerase is thought to be essential to the stabilization of telomere length and for overcoming replicative senescence, which may lead to cellular immortality (4) Telomerase is activated in the vast majority of cancer cells (5,6), including those of pancreatic cancer (7), but is usually repressed in most normal somatic tissue. This suggests that telomerase activation may be a critical step in the progression to cellular immortality and carcinogenesis. The relative tumor selective expression of telomerase has made the enzyme an appropriate target for the development of new anticancer therapies. Telomerase consists of a protein reverse transcriptase, hTERT, and an RNA compone...

Non-coding RNA is still one of the most popular fields in biology research. In recent years, people paid more attention to the roles of H19 in lung diseases, which expressed abnormally in various pathological process. Therefore, this review focus on the regulatory role of H19 in asthma, pulmonary arterial hypertension (PAH), idiopathic pulmonary fibrosis (IPF), lung injury, pneumonia, lung cancer, etc. And the potential therapeutic agents and molecular treatments of H19 are collected. The aim is to demonstrate its underlying mechanism in pulmonary diseases and to guide the basic research targeting H19 into clinical drug translation.

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