Long non-coding RNA COL4A2-AS1 facilitates cell proliferation and glycolysis of colorectal cancer cells via miR-20b-5p/hypoxia inducible factor 1 alpha subunit axis.

Long non-coding RNAs (lncRNAs) have critical functions in tumorigenesis and progression of colorectal cancer (CRC). The role of lncRNA COL4A2-AS1 (COL4A2-AS1) lacks system investigation. The current study comprehensively analyzed the expression, biological functions, and mechanism of COL4A2-AS1 in CRC through performing real-time quantitative PCR (RT-qPCR), Western blot, cell transfection, cell colony assay, MTT assay, flow cytometry and dual-luciferase reporter system assays. A xenograft model of CRC was constructed to further verify the function of COL4A2-AS1 in CRC progression in vivo. The data revealed an upregulated expression of COL4A2-AS1 in CRC tissues and cell lines than paired adjacent tissues and normal cell line. Silencing COL4A2-AS1 inhibited proliferation, aerobic glycolysis, and promoted apoptosis of CRC cells in vivo and in vitro. However, overexpression of COL4A2-AS1 significantly promoted CRC cell proliferation and aerobic glycolysis. In CRC cells, miR-20b-5p was sponged by COL4A2-AS1 and hypoxia-inducible factor 1 alpha subunit (HIF1A). Restoration of HIF1A expression reversed the inhibitory effects of silencing COL4A2-AS1 on aerobic glycolysis and proliferation of CRC cells. The current findings showed that COL4A2-AS1 promoted the proliferation, and aerobic glycolysis of CRC cells potentially through modulating the miR-20b-5p/HIF1A axis.

Photosensitized Degradation of Amitriptyline and Its Active Metabolite Nortriptyline in Aqueous Fulvic Acid Solution.

Amitriptyline is a frequently prescribed tricyclic antidepressant. Although amitriptyline and its active metabolite, nortriptyline, have been widely detected in natural waters, their environmental fate due to photodegradation is poorly understood. Here we describe a study conducted to investigate the photodegradation of amitriptyline and its active metabolite under simulated sunlight. Neither amitriptyline nor nortriptyline underwent direct photodegradation, but rapid photosensitized degradation did occur in fulvic acid (FA) solutions. The photodegradation of amitriptyline and nortriptyline followed pseudo-first-order kinetics with rate constants 0.24 and 0.16 h, respectively, at pH 8.0 in air-saturated FA solutions. The photodegradation of the substrates increased markedly with pH. The deprotonation of amitriptyline and nortriptyline facilitated the availability of nonbonding electrons on nitrogen (N-electrons). The excited triplet state of FA (FA*) was verified as the main reactive species responsible for the photosensitized degradation. An electron transfer mechanism for the interaction between substrates and FA* was proposed on the basis of a series of quenching experiments, kinetic model and photoproducts determination. Demethylation at the α-carbon of amine and hydroxylation were two primary photochemical processes initiated by the electron transfer reaction in the air-saturated FA solution; these were followed by generation of demethyl amine and mono-hydroxylation isomers. Our results suggest that indirect photodegradation is an important elimination process for amitriptyline and its active metabolite in natural waters.