Mesenchymal stem cell (MSC) aging seriously affects its function in stem cell transplantation for treatment. Extensive studies have focused on how to inhibit senescence in MSCs. However, the mechanism of senescence in MSC was not clear. In this study, we used D-galactose to induce MSC aging. Then we found that the number of aging cells was increased compared with untreated MSCs. We discovered that ascorbic acid could inhibit the production of reactive oxygen species (ROS) and activation of AKT/mTOR signaling in MSCs caused by D-galactose. Especially, when treated together with a ROS scavenger or AKT inhibitor, the senescent cells were obviously decreased in D-galactose-induced MSCs. Taken together, we identify that ascorbic acid owns the potential to inhibit the senescence of MSCs through ROS and Akt/mTOR signaling. Together, our data supports that ascorbic acid can be used to prevent MSCs from senescence, which can enhance the efficiency of stem cell transplantation in the clinic.
Abstract. The aim of the present study was to investigate the function of long chain non-coding RNA (lncRNA) in breast cancer cells. Quantitative polymerase chain reaction was used to measure mRNA expression levels in breast cancer tissues, adjacent tissues and in MCF-7 breast cancer cells. Western blot analysis was used to determine the protein expression levels. In addition, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was employed to measure the rates of cell proliferation. The invasion and migration of the MCF-7 cells were examined using a Transwell ® assay. The expression levels of lncRNA-AK058003 were increased significantly in the breast cancer tissues and were found to strongly correlate with the severity of the breast cancer clinical stage. Bioinformatics analysis revealed that the γ-synuclein gene (SNCG) may be a target gene regulated by lncRNA-AK058003. Thus, lncRNA-AK058803 was downregulated using small interfering RNA, and the mRNA and protein expression levels of SNCG were shown to be significantly reduced. Furthermore, the proliferation, invasion and migration rates of the MCF-7 breast cancer cells were significantly reduced. Therefore, the results demonstrated that unregulated lncRNA-AK058003 in breast cancer cells promotes cancer cell proliferation, invasion and metastasis via the regulation of SNCG expression. IntroductionBreast cancer is a common clinical condition with increasing morbidity and high mortality rates (1). Previous studies have suggested that the development of breast cancer is associated with inactivated tumor suppressor genes, dysfunctional signaling transduction pathways and other malfunctioning molecular signaling processes (2-4). With the development of chemotherapy, hormonal therapy, immunotherapy, gene therapy and other treatment technologies, the long-term survival of breast cancer patients has become possible. Breast cancer patients continue to succumb to the disease due to tumor metastasis, drug resistance and other reasons including hemorrhage, infection and recurrence (5). Therefore, finding novel biomarkers for use in the early diagnosis and treatment of breast cancer has become increasingly studied.A high-throughput sequencing study revealed the existence of types of non-coding RNA in gene transcripts, including small non-coding RNA and long non-coding (lnc)RNA (6). LncRNA has a length of >200 nucleotides and a similar structure to mRNA, including a 5' cap and poly-A tail. However, lncRNA is unable to encode proteins due to the absence of an open reading frame (7). Increasing numbers of studies have indicated that lncRNA may play an important role in various cellular processes, including cell differentiation, proliferation and apoptosis (8,9). Notably, a previous study revealed a novel function of lncRNA in the development of prostate cancer (10). In addition, long non-coding homeobox antisense intergenic RNA is reported to be a highly valuable clinical biomarker for the prognosis and early diagnosis of ovarian cancer (11).The primary functio...
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