Tumour-suppressive miRNA-26a-5p and miR-26b-5p inhibit cell aggressiveness by regulating PLOD2 in bladder cancer.

BACKGROUND: Previous studies have revealed that miR-26a-5p and miR-26b-5p act as tumour suppressors in various types of cancer tissues. Here, we aimed to investigate the functional roles of these miRNAs and to identify their regulatory targets in bladder cancer (BC). METHODS: We performed functional assays in BC cells using transfection of mature microRNAs (miRNAs). In silico and luciferase reporter analyses were applied to identify target genes of these miRNAs. The overall survival (OS) of patients with BC was evaluated by the Kaplan-Meier method. RESULTS: miR-26a-5p and miR-26b-5p were significantly downregulated in BC tissues. Restoration of these miRNAs inhibited cell migration and invasion in BC. The gene encoding procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a collagen crosslinking enzyme, was directly regulated by miR-26a-5p and miR-26b-5p. Kaplan-Meier analysis revealed that patients with high PLOD2 expression had significantly shorter OS compared with those with low PLOD2 expression (P=0.0153). CONCLUSIONS: PLOD2, which is associated with the stiffness of the extracellular matrix, was directly regulated by miR-26a-5p and miR-26b-5p and may be a good prognostic marker in patients with BC.

Orbital cortex neuronal responses during an odor-based conditioned associative task in rats.

Neuronal activity in the rat orbital cortex during discrimination of various odors [five volatile organic compounds (acetophenone, isoamyl acetate, cyclohexanone, p-cymene and 1,8-cineole), and food- and cosmetic-related odorants (black pepper, cheese, rose and perfume)] and other conditioned sensory stimuli (tones, light and air puff) was recorded and compared with behavioral responses to the same odors (black pepper, cheese, rose and perfume). In a neurophysiological study, the rats were trained to lick a spout that protruded close to its mouth to obtain sucrose or intracranial self-stimulation reward after presentation of conditioned stimuli. Of 150 orbital cortex neurons recorded during the task, 65 responded to one or more types of sensory stimuli. Of these, 73.8% (48/65) responded during presentation of an odor. Although the mean breadth of responsiveness (entropy) of the olfactory neurons based on the responses to five volatile organic compounds and air (control) was rather high (0.795), these stimuli were well discriminated in an odor space resulting from multidimensional scaling using Pearson's correlation coefficients between the stimuli. In a behavioral study, a rat was housed in an equilateral octagonal cage, with free access to food and choice among eight levers, four of which elicited only water (no odor, controls), and four of which elicited both water and one of four odors (black pepper, cheese, rose or perfume). Lever presses for each odor and control were counted. Distributions of these five stimuli (four odors and air) in an odor space derived from the multidimensional scaling using Pearson's correlation coefficients based on behavioral responses were very similar to those based on neuronal responses to the same five stimuli. Furthermore, Pearson's correlation coefficients between the same five stimuli based on the neuronal responses and those based on behavioral responses were significantly correlated. The results demonstrated a pivotal role of the rat orbital cortex in olfactory sensory processing and suggest that the orbital cortex is important in the manifestation of various motivated behaviors of the animals, including odor-guided motivational behaviors (odor preference).