MicroRNA-384 inhibits nasopharyngeal carcinoma growth and metastasis via binding to Smad5 and suppressing the Wnt/β-catenin axis

Nasopharyngeal carcinoma (NPC) is a major otorhinolaryngological disease with limited effective therapeutic options. This work focused on the function of microRNA-384 (miR-384) on the NPC pathogenesis and the molecules involved. miR-384 expression in cancer tissues and cells was detected. Gain- and loss-of-functions of miR-384 were performed to identify its role in NPC progression. The target mRNA of miR-384 was predicted on an online system and validated through a luciferase reporter assay. The activity of Wnt/β-catenin signaling was detected. Consequently, miR-384 was found to be poorly expressed in NPC tissues and cell lines and was linked to unfavorable survival rates in patients. Overexpression of miR-384 in 6-10B cells suppressed growth, migration, invasion and resistance to apoptosis of cells, but inverse trends were presented in C6661 cells where miR-384 was downregulated. miR-384 targeted Smad5 mRNA. Upregulation of Smad5 counteracted the roles of miR-384 mimic in cells. The NPC-inhibiting effects of miR-384 mimic were also blocked by Wnt/β-catenin activation. To conclude, miR-384 targets Smad5 and inactivates the Wnt/β-catenin pathway, which exerts a suppressing role in NPC cell behaviors as well as tumor growth in vivo. The findings may offer novel thoughts into NPC therapy.

The Regulation of Bone Morphogenetic Protein/Smads Signaling Pathway in Spinal Cord Injury

The incidence of spinal cord injury (SCI) increases year by year. SCI is characterized as high disability rate and poor prognosis. BMP/Smads signaling participates in the formation of osteoblasts and renal failure. This article will explore the regulation of BMP/Smads signaling pathway in SCI. Wistar rats were divided into control group; SCI group; and BMP-2 treatment group that were treated by tail vein injection of BMP-2 antisense oligonucleotide BMP-2 phosphorothioate AODN at 30 min after modeling. Real-time PCR and Western blot were used to detect BMP-2, Smad1, and Smad5 expressions. Hematoxylin-eosin (HE) staining was applied to analyze the change of SCI in each group. Immunohistochemistry (IHC) was selected to test BMPR Ia expression. Basso, Beattie Bresnahan-cocomotor rating scale (BBB) scale and Reuter score were compared. Enzyme-linked immunosorbent assay (ELISA) was adopted to detect TNF-α and Interleukin-2 (IL-2) expressions. Compared with the control group, BMP-2, Smad1, and Smad5 mRNA and protein expressions increased, BBB score declined, Reuter score elevated, and TNF-α and IL-2 secretion enhanced in the SCI group (P < 0.05). HE staining showed spinal cord injury, and IHC exhibited increased expression of BMPR Ia. The TGF-β treatment group significantly reduced the expressions of BMP-2, Smad1, and Smad5 mRNA and protein, increased BBB score, reduced Reuter score, and weakened the secretions of TNF-α and IL-2 (P < 0.05). HE staining demonstrated decreased reduction of spinal cord tissue and declined expression of BMPR Ia. SCI activated BMP/Smads signaling pathway, up-regulated BMPR Ia expression, and promoted inflammation. Regulation of BMP/Smads signaling pathway can downregulate BMPR Ia expression and inhibit inflammation to effectively relieve SCI.