LncRNA CASC2 Alleviates the Progression of Diabetic Nephropathy by Regulating the miR-144/SOCS2 Signalling Axis

Abstract

<b><i>Background:</i></b> Diabetic nephropathy constitutes a large proportion of end-stage kidney failure in diabetic patients. However, the underlying molecular mechanisms remain unclear. <b><i>Methods:</i></b> Db/db diabetic mouse models and high glucose (HG)-induced human renal mesangial cells (HRMCs) were used as research models in vivo and in vitro. The expression of cancer susceptibility candidate 2 (CASC2) was quantified by qRT-PCR. The regulatory role of CASC2 in cell apoptosis, inflammatory factor release, and fibrosis was verified by flow cytometry, qRT-PCR, and Western blot assay, respectively. The bioinformatics prediction software DIANA and starBase v2.0 were used to predict the putative binding sites. The interactions among CASC2, miR-144, and SOCS2 were explored by the luciferase assay and Western bolt assay. <b><i>Results:</i></b> The expression of CASC2 in diabetic mouse models and HG-induced HRMCs was lower than that in the control (<i>p</i> < 0.05). Overexpression of CASC2 resulted in a decrease in the apoptosis rate, inflammatory factor release (TNF-α, IL-6, and IL-1β), expression of cleaved caspase-3, and fibrotic proteins (fibronectin, Col-IV, and TGF-β1) and an increase in Bcl-2 expression. Inhibition of CASC2 caused increased expression of miR-144. Furthermore, mechanistic investigations confirmed that activation of the miR-144/SOCS2 regulatory loop by overexpression of miR‐144 reversed the in vitro effects of CASC2 on inhibiting cell apoptosis, inflammatory factor release, and fibrosis. In addition, simultaneous overexpression of miR-144 and SOCS2 further increased the inhibition of cell apoptosis, inflammatory factor release, and fibrosis by CASC2. <b><i>Conclusion:</i></b> CASC2 could alleviate the degree and process of apoptosis, inflammation, and fibrosis in diabetic nephropathic models by regulating the miR-144/SOCS2 axis.

Long non-coding RNA CASC2 restrains high glucose-induced proliferation, inflammation and fibrosis in human glomerular mesangial cells through mediating miR-135a-5p/TIMP3 axis and JNK signaling

“…Li et al found that lncRNA KCNQ1OT1 interference alleviates HG-induced proliferation, oxidative stress and deposition of ECM in HMCs through regulating miR-18b/HMGA2 signaling [ 7 ]. As for lncRNA CASC2, Min et al found that CASC2 attenuates DN development by targeting miR-144/SOCS2 axis [ 9 ]. Zhang et al found that CASC2 is down-regulated in the serum samples of DN patients and HG-treated HMCs, and CASC2 inhibits HG-mediated proliferation, oxidative stress and the accumulation of ECM in HMCs by regulating miR-133b/FOXP1 signaling [ 10 ].…”

“…Wang et al demonstrated that lncRNA CTBP1-AS2 attenuates HG-mediated oxidative stress, the deposition of ECM, and inflammatory response in mesangial cells by sponging miR-155-5p to induce FOXO1 expression [ 8 ]. lncRNA cancer susceptibility candidate 2 (CASC2) is reported to suppress DN progression through different signaling axes [ 9 , 10 ]. In this study, the working mechanism of CASC2 in DN progression was further explored.…”

LncRNA CASC2 is involved in the development of chronic obstructive pulmonary disease via targeting miR-18a-5p/IGF1 axis

“…Consistently, low expression of CASC2 is identified in a diabetic nephropathy rat model; upregulation of CASC2 can inhibit the inflammatory factor release and further relieve the disease process. 9 Another study also reported the low expression level of CASC2 during the development of ALI, and LPS-induced inflammatory response in the ALI cell model can be suppressed by CASC2 upregulation. 10 These findings supported our results about the potential role of CASC2 in COPD.…”

“…Upregulation of CASC2 can inhibit the release of inflammatory factors and further relieve the disease process. 9 Another study has also reported the low expression level of CASC2 during the development of acute lung injury (ALI). Upregulation of CASC2 can alleviate the lipopolysaccharide (LPS)-induced inflammatory response in the ALI cell model.…”

Differential Expression of lncRNA CASC2 in the Serum of Childhood Asthma and Its Role in Airway Smooth Muscle Cells Proliferation and Migration

“…As Min et al reported, upregulation of CASC2 suppressed inflammatory factor release in high glucose (HG)-induced human renal mesangial cells, thus relieving the progression of diabetic nephropathy. 29 In acute lung injury, CASC2 can inhibit the inflammatory response of cell models. 11 In light of the anti-inflammatory action of CASC2 in asthma cell models, we deduced that CASC2 might be involved in the progression of asthma via regulating Th1/Th2 imbalance and inflammatory responses.…”