Retracted: MicroRNA‐140‐5p elevates cerebral protection of dexmedetomidine against hypoxic–ischaemic brain damage via the Wnt/β‐catenin signalling pathway

Abstract

Hypoxia–ischaemia (HI) remains a major cause of foetal brain damage presented a scarcity of effective therapeutic approaches. Dexmedetomidine (DEX) and microRNA‐140‐5p (miR‐140‐5p) have been highlighted due to its potentially significant role in the treatment of cerebral ischaemia. This study was to investigate the role by which miR‐140‐5p provides cerebral protection using DEX to treat hypoxic–ischaemic brain damage (HIBD) in neonatal rats via the Wnt/β‐catenin signalling pathway. The HIBD rat models were established and allocated into various groups with different treatment plans, and eight SD rats into sham group. The learning and memory ability of the rats was assessed. Apoptosis and pathological changes in the hippocampus CA1 region and expressions of the related genes of the Wnt/β‐catenin signalling pathway as well as the genes responsible of apoptosis were detected. Compared with the sham group, the parameters of weight, length growth, weight ratio between hemispheres, the rate of reaching standard, as well as Bcl‐2 expressions, were all increased. Furthermore, observations of increased levels of cerebral infarction volume, total mortality rate, response times, total response duration, expressions of Wnt1, β‐catenin, TCF‐4, E‐cadherin, apoptosis rate of neurons, and Bax expression were elevated. Following DEX treatment, the symptoms exhibited by HIBD rats were ameliorated. miR‐140‐5p and si‐Wnt1 were noted to attenuate the progression of HIBD. Our study demonstrates that miR‐140‐5p promotes the cerebral protective effects of DEX against HIBD in neonatal rats by targeting the Wnt1 gene through via the negative regulation of the Wnt/β‐catenin signalling pathway.

Neuroprotective Effects of microRNA-140-5p on Ischemic Stroke in Mice via its Regulation on the TLR4/NF-κB Axis

“…For example, miR-7a-5p was demonstrated to therapeutically reduce the brain damage and disability caused by ischemic stroke [37]. Additionally, consistent with the observations of our study, miR-140-5p has been highlighted due to its promotion role in the cerebral protective effects of dexmedetomidine against hypoxic-ischemic brain damage (HIBD) in neonatal rats [38]. Furthermore, there is existing data that suggests that miR-140-5p suppresses the tumor growth and progression of hepatocellular carcinoma, tongue cancer, and cervical cancer [28,39,40].…”

Isoflurane-induced expression of miR-140-5p aggravates neurotoxicity in diabetic rats by targeting SNX12

“…In our study, knockdown of miR-140-5p decreased the expression of Cleaved Caspase-3 and increased the expression of Bcl-2 to inhibit hippocampal neuronal apoptosis in diabetic rats with isoflurane anesthesia. Wnt1 was identified as a target of miR-140-5p in neonatal rats for cerebral protection (Han et al, 2018) or in dental pulp stem cells for odontoblastic differentiation (Lu et al, 2019). In the present study, SNX12 was identified as a new target of miR-140-5p.…”

“…MiR-140-5p was identified as a tumor suppressor in gastric cancer (Fang et al, 2017), and regulates odontoblastic differentiation (Lu et al, 2019). More recently, miR-140-5p was shown to protect against hypoxic-ischaemic brain damage via promotion of learning and memory abilities (Han et al, 2018). In addition, a study has shown that miR-140-5p was increased 6 hr after isoflurane treatment (Luo et al, 2015).…”

miR-140-5p inhibits the proliferation and enhances the efficacy of doxorubicin to breast cancer stem cells by targeting Wnt1

“…However, such effect is diminished when the 3′UTR of the Wnt1 sequence is mutated. Consistently, Han et al revealed that miR-140-5p could target and inhibit the Wnt1 gene, thus highlighting the negative regulation of the Wnt/β-catenin signaling pathway in hypoxia [21].…”