ABSTRACT
The colorectal cancer (CRC) dictates a common malignancy with high recurrence rate. Long non-coding RNAs (lncRNAs) belong to a class of regulatory factors involved in multiple cancers. In current work, we have uncovered a novel lncRNA named TSLC8. TSLC8 was dramatically downregulated in CRC samples and cell lines. Reintroduction of TSLC8 inhibited tumor sphere formation and viability in CRC cells. In vivo experiments further confirmed the tumor suppressive function of TSLC8. Ectopic TSLC8 expression elevates puma abundance whereas this effect is mediated by TSLC8-puma binding and stabilization. FOXO1 can transcriptionally induce TSLC8 expression. Epigenetic investigation suggested that TSLC8 locus was hypermethylated in CRC leading to diminished TSLC8 expression. Our current work has identified a novel tumor suppressive function of TSLC8, whose reduced expression may facilitate malignant phenotypes during CRC progression.
Subject(s)
Apoptosis Regulatory Proteins/biosynthesis , Colorectal Neoplasms/metabolism , Proto-Oncogene Proteins/biosynthesis , RNA, Long Noncoding/biosynthesis , Animals , Apoptosis Regulatory Proteins/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/prevention & control , Female , HCT116 Cells , Humans , Mice , Mice, Nude , Proto-Oncogene Proteins/genetics , RNA, Long Noncoding/genetics , Xenograft Model Antitumor Assays/methodsABSTRACT
The purpose of this study was to investigate the protective effects of Saikosaponin a (SSa), a triterpene saponin derived from Radix bupleuri, on lipopolysaccharide (LPS)-induced acute lung injury (ALI) using a murine model. The mice were given SSa 1 h after intranasal instillation of LPS. Then, lung histopathological examination, the wet/dry (W/D) ratio, myeloperoxidase (MPO), and inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were detected in this study. The results showed that SSa reduced lung pathological injury induced by LPS. Furthermore, LPS-induced lung W/D ratio, MPO activity, and inflammatory cytokines TNF-α and IL-1ß in BALF were significantly inhibited by SSa. In addition, SSa suppressed LPS-induced NF-κB activation and NLRP3 inflammasome expression. In conclusion, we found that SSa played a critical anti-inflammatory effect through inhibition of NF-κB and NLRP3 signaling pathways and protected against LPS-induced ALI.
