microRNA‑124‑3p inhibits the progression of congenital hypothyroidism via targeting programmed cell death protein 6

Abstract

Abstract. The incidence of congenital hypothyroidism (CH) in newborn infants ranges from 1 in 3,000 to 1 in 4,000. Previous studies have indicated the neuroprotective role of microRNA (miR)-124-3p, however the expression and role of miR-124-3p in CH remain unclear. Therefore, the present study was performed to investigate the role and precise molecular mechanism of miR-124-3p in CH. Propylthiouracil (50 mg/day) was injected into the stomach of pregnant rats from gestational day 15 until parturition in order to establish a thyroid hypofunction model. Newborn rats were divided into the following four groups: The control group; the thyroid hypofunction group; the miR-124-3p mimic group; and the miR-124-3p negative control group. Reverse transcription-quantitative polymerase chain reaction indicated that miR-124-3p was significantly decreased in the hippocampus of the thyroid hypofunction group compared with the control group. Bioinformatics software was used to predict mRNA targets recognized by miR-124-3p and the programmed cell death protein 6 (PDCD6) 3' untranslated region (UTR) was demonstrated to exhibit the seed sequence of miR-124-3p. The interaction between miRNA-124-3p and PDCD6 was then verified using a dual-luciferase reporter assay system. PDCD6 expression was significantly increased in the hippocampus of rats with CH compared with the control group. Flow cytometry was performed to investigate the effects of miR-124-3p on neuronal cell apoptosis and the results indicated that the apoptosis rate in the thyroid hypofunction group was significantly increased compared with the control group; this increase was reversed by transfection with miR-124-3p mimics. Western blot analysis was used to detect the levels of cleaved poly [ADP-ribose] polymerase (PARP), full-length PARP, caspase-3, B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) proteins. The results indicated that the expression of cleaved PARP, caspase-3 and Bax protein were significantly increased and the expression of full-length PARP and Bcl-2 protein was significantly decreased compared with the control group. These effects were reversed by miRNA-124-3p mimic transfection. Taken together, the results of the present study demonstrate that miRNA-124-3p serves a protective role in CH via targeting PDCD6.

MicroRNA‑1236‑3p/translationally controlled tumor protein (TPT1) axis participates in congenital hypothyroidism progression by regulating neuronal apoptosis

“…In addition, TH deficiency can lead to hippocampal neuronal cell injury and cell apoptosis (33). miRNAs have been revealed to serve a critical role in diseases associated with the nervous system, including autoimmune neuroinflammation (34), Alzheimer's disease (35), Parkinson's disease (36) and CH (16). A previous study has reported that miR-124 can protect neurons from apoptosis in rat models of hypothyroidism (16).…”

“…miRNAs have been revealed to serve a critical role in diseases associated with the nervous system, including autoimmune neuroinflammation (34), Alzheimer's disease (35), Parkinson's disease (36) and CH (16). A previous study has reported that miR-124 can protect neurons from apoptosis in rat models of hypothyroidism (16). In the case of miR-1236, it has been reported to induce cell apoptosis in bladder cancer cells by inhibiting p21 expression (37).…”

“…For the treatment of CH pups, animals were anesthetized with an intraperitoneal injection of 2% sodium pentobarbital (40 mg/kg). Newborn rats (12 days old) were subsequently fixed on a stereotaxic apparatus and their skulls were opened at 1.0 mm from the former fontanel and 1.7 mm from the mid-line (16). A micro syringe was then inserted vertically into the left lateral ventricle (bregma: −0.58 mm; dorsoventral: 2.1 mm; lateral: 1.2 mm) and pups were injected with miR-1236-3p inhibitor control solution (5 µl; 1 nmol/l), miR-1236-3p inhibitor (5 µl; 1 nmol/l) or miR-1236-3p inhibitor (5 µl; 1 nmol/l) + TPT1-siRNA solution (5 µl; 1 nmol/l) as previously described (25).…”

“…Mature miRNA directly bind to mRNAs to regulate their expression (15). Recent research has suggested that miRNAs participate widely in diseases involving the nervous system, including congenital hypothyroidism (16). For example, a previous study has demonstrated that miR-124 inhibits the progression of congenital hypothyroidism (16).…”

“…Recent research has suggested that miRNAs participate widely in diseases involving the nervous system, including congenital hypothyroidism (16). For example, a previous study has demonstrated that miR-124 inhibits the progression of congenital hypothyroidism (16). Previous studies have revealed that miR-1236 can serve different roles in a tissue- or physiological-dependent manners.…”