MiR-135 post-transcriptionally regulates FOXO1 expression and promotes cell proliferation in human malignant melanoma cells.

Malignant melanoma is the deadliest form of all skin cancers. Recently, microRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by targeted repression of transcription and translation and play essential roles during cancer development. Our study showed that miR-135a is upregulated in malignant melanoma tissues and cell lines by using Real-time PCR assay. Enforced expression of miR-135a in malignant melanoma cells promotes cell proliferation, tumorigenicity, and cell cycle progression, whereas inhibition of miR-135a reverses the function. Additionally, we demonstrated FOXO1 is a direct target of miR-135a and transcriptionally down-regulated by miR-135a. Ectopic expression of miR-135a led to downregulation of the FOXO1 protein, resulting in upregulation of Cyclin D1, and downregulation of P21(Cip1) and P27(Kip1) through AKT pathway. Our findings suggested that miR-135a represents a potential onco-miRNA and plays an important role in malignant melanoma progression by suppressing FOXO1 expression.

Effects of ketamine on lipopolysaccharide-induced depressive-like behavior and the expression of inflammatory cytokines in the rat prefrontal cortex.

The present study was designed to investigate the effects of ketamine on lipopolysaccharide (LPS)-induced depressive-like behavior and the expression of inflammatory cytokines in the rat prefrontal cortex. Thirty male Wistar rats were randomly divided into 3 groups (n=10): saline group (S group), LPS only group (L group) and LPS plus ketamine group (LK group). A forced swimming test (FST) was performed. On the first day, rats were placed into water for 15 min. Twenty-four hours later, rats were treated again as in the first test for a 5 min session, and the immobility time was recorded. The prefrontal cortex was harvested for the determination of the interleukin (IL)­1ß, IL-6 and IL-10 levels. Compared with the S group, rats in the L group had significantly increased immobility time in the FST and expression of IL-1ß and IL-6, and significantly decreased expression of IL-10 in the prefrontal cortex (P<0.05). However, rats in the LK group had significantly decreased immobility times in the FST and expression of IL-1ß and IL-6, and significantly increased expression of IL-10 in the prefrontal cortex compared with the L group (P<0.05). Ketamine can alleviate LPS-induced depressive-like behavior, and its effect is likely associated with changes in the expression of inflammatory cytokines in the rat prefrontal cortex.

Intrathecal administration of Cav3.2 and Cav3.3 antisense oligonucleotide reverses tactile allodynia and thermal hyperalgesia in rats following chronic compression of dorsal root of ganglion.

AIM: The present study aimed to elucidate the role of T-subtype calcium channels (Cav3.1, Cav3.2, and Cav3.3) in the pathogenesis of neuropathic pain at spinal level. METHODS: The chronic compression of the dorsal root ganglion (CCD) rat model was adopted. The antisense oligonucleotide of Cav3.1, Cav3.2, and Cav3.3 or normal saline (NS) were intrathecally administered twice per day from the first day to the fourth day after operation. Paw mechanical withdrawal threshold and paw thermal withdrawal latency were measured to evaluate the tactile allodynia and thermal hyperalgesia, respectively. RESULTS: CCD rats developed reliable tactile allodynia and thermal hyperalgesia after operation. Intrathecal administration of antisense oligonucleotide of Cav3.2 and Cav3.3 significantly relieved tactile allodynia and thermal hyperalgesia in CCD rats, but not Cav3.1. CONCLUSION: Cav3.2 and Cav3.3 subtype calcium channels in the spinal cord may play an important role in the pathogenesis of neuropathic pain, which may contribute to the management of the neuropathic pain.