microRNA-130a Promotes Human Keratinocyte Viability and Migration and Inhibits Apoptosis Through Direct Regulation of STK40-Mediated NF-κB Pathway and Indirect Regulation of SOX9-Meditated JNK/MAPK Pathway: A Potential Role in Psoriasis

Abstract

Psoriasis is a chronic inflammatory skin disorder. The aim of this study was to determine a potential role of microRNA (miR)-130a in psoriasis, and underlying mechanism. Expression levels of miR-130a in psoriasis specimens and normal skin tissues were analyzed. MiR-130a mimic, inhibitor, miR-control, small interfering RNA (siRNA) specific serine/threonine kinase 40 (STK40), or sex-determining region Y chromosome-box 9 (SOX9) were transfected to human keratinocyte HaCaT cells, respectively. After transfection, the cell viability, apoptosis, and migration were determined. Luciferase reporter assay, quantitative reverse transcription-polymerase chain reaction, and western blot were performed to explore whether STK40 was a target of miR-130a. The effects of aberrant expressions of miR-130a, STK40, or SOX9 on key proteins of NF-κB and c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) pathway were assessed. The miR-130a levels were significantly higher in patients with psoriasis compared to the healthy controls (p < 0.01). Overexpressing miR-130a strikingly promoted HaCaT cell viability and migration and inhibited apoptosis (p < 0.01 or p < 0.05). We confirmed that STK40 was a direct target of miR-130a, and STK40 was involved in miR-130a-induced cell functions. Overexpressing miR-130a significantly upregulated NF-κB p65, SOX9, p-c-Jun, p-JNK, and p-p38MAPK proteins and silencing miR-130a downregulated them. In addition, silencing STK40 alleviated the effects of anti-miR-130a on SOX9 expression. Furthermore, silencing SOX9 also decreased levels of p-c-Jun, p-JNK, and p-p38MAPK proteins. MiR-130a regulates human keratinocyte HaCaT viability, migration and apoptosis might be by direct regulation of STK40-mediated NF-κB pathway and by indirect regulation of SOX9-mediated downstream JNK/MAPK signaling pathway.

Plasma MicroRNA Expression Profiles in Psoriasis

“…The VEGF signaling pathway plays an important role in psoriasis [51]. Moreover, molecules associated with MAPK have been reported to be upregulated in the blood of psoriasis patients [52], and the p38 MAPK pathway is involved in psoriasis [53]. In addition, the WNT pathway is involved in skin inflammation in psoriasis patients [54].…”

Deletion of Stk40 impairs definitive erythropoiesis in the mouse fetal liver

“…36 Recently, STK40 was reported to suppress the NF- κ B pathway involved in human keratinocyte viability, migration and apoptosis. 37 Therefore, Stk40 may have a conserved inhibitory role of cytokine-induced NF- κ B signaling independent of cell types and contexts. Multiple studies have demonstrated that TNF- α inhibits erythropoiesis and causes anemia in human.…”

Research progress on the relationship between zinc deficiency, related microRNAs, and esophageal carcinoma

“…STK40 is a negative regulator of nuclear factor kappa B (NF-κB)-mediated transcription and acts as a tumor suppressor directly targeted by miR-31. [36][37][38] Taccioli et al simulated the features of human EC using a rat model and examined the mechanism whereby Zn regulates miR-31 expression to promote EC progression. Zn deficiency induced the overexpression of miR-31 in a rat EC model.…”

“…In summary, miR‐223 is upregulated and is accompanied by the downregulation of its target tumor suppressor genes FBXW7, PARP1 , and SMARCD1 in EC. STK40 is a negative regulator of nuclear factor kappa B (NF‐κB)‐mediated transcription and acts as a tumor suppressor directly targeted by miR‐31 …”