Dataset Information

Downregulation of microRNA-125a is involved in intervertebral disc degeneration by targeting pro-apoptotic Bcl-2 antagonist killer 1.

ABSTRACT: Objectives:To investigate the role of the microRNA-125a (miR-125a) and BAK1 in intervertebral disc degeneration (IDD). Materials and Methods:Degenerative lumbar nucleus pulposus (NP) tissues were obtained from 193 patients who underwent resection, and normal controls consisted of normal NP tissues from 32 patients with traumatic lumbar fracture in our hospital. All patients were graded according to the Pfirrmann criteria. QRT-PCR was used to detect the expression of miR-125a and BAK1, and apoptosis of NP tissues detected by TUNEL staining. After isolation of non- degenerative and degenerative nucleus pulposus cells (NPCs), the targeting relationship between miR-125a and BAK1 was verified by dual luciferase reporter gene assay. Flow cytometry was determined the NPCs apoptosis, and Western blot to measure the expressions of BAK1, Caspase-3, Bax and Bcl-2. Results:MiR-125a was reduced while BAK1 was elevated in IDD patients with the increase of Pfirrmann grade. Besides, miRNA-125a was negatively correlated to the NPCs apoptosis, while BAK1 mRNA was positively correlated to cell apoptosis. Additionally, BAK1 is the target gene of miRNA-125a. When transfection of miR-125a mimics in vitro, the apoptosis of NPCs were inhibited, with the down-regulation of BAK1, Caspase-3, and Bax, and the upregulation of Bcl-2. In addition, siBAK1 can reverse the pro-apoptosis function of miR-125a inhibitors in NPCs. Conclusion:miRNA-125a may regulate the apoptosis status of the NPCs by inhibiting the expression of its target gene BAK1, which provided a potential strategy for further development of IDD therapies.

SUBMITTER: Liu P

PROVIDER: S-EPMC5749361 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Downregulation of microRNA-125a is involved in intervertebral disc degeneration by targeting pro-apoptotic Bcl-2 antagonist killer 1.

Liu Ping P Chang Feng F Zhang Ting T Gao Gang G Yu Chen C Ding Sheng-Qiang SQ Zuo Gen-Le GL Huang Xin-Hu XH

Iranian journal of basic medical sciences 20171101 11

<h4>Objectives</h4>To investigate the role of the microRNA-125a (miR-125a) and BAK1 in intervertebral disc degeneration (IDD).<h4>Materials and methods</h4>Degenerative lumbar nucleus pulposus (NP) tissues were obtained from 193 patients who underwent resection, and normal controls consisted of normal NP tissues from 32 patients with traumatic lumbar fracture in our hospital. All patients were graded according to the Pfirrmann criteria. QRT-PCR was used to detect the expression of miR-125a and B ...[more]

PMID: 29299204

Similar Datasets

Project description:Background contextDisc degeneration (DD) is a multifaceted chronic process that alters the structure and function of the intervertebral discs and can lead to painful conditions. The pathophysiology of degeneration is not well understood, but previous studies suggest that certain genetic polymorphisms may be important contributing factors leading to an increased risk of DD.PurposeTo review the genetic factors in DD with a focus on polymorphisms and their putative role in the pathophysiology of degeneration. Elucidating the genetic components that are associated with degeneration could provide insights into the mechanism of the process. Furthermore, defining these relationships and eventually using them in a clinical setting may allow an identification and early intervention for those who are at a high risk for painful DD.Study designLiterature review.MethodsThis literature review focused on the studies concerning genetic polymorphisms and their associations with DD.ResultsGenetic polymorphisms in 20 genes have been analyzed in association with DD, including vitamin D receptor, growth differentiation factor 5 (GDF5), aggrecan, collagen Types I, IX, and XI, fibronectin, hyaluronan and proteoglycan link protein 1 (HAPLN1), thrombospondin, cartilage intermediate layer protein (CILP), asporin, MMP1, 2, and 3, parkinson protein 2, E3 ubiquitin protein ligase (PARK2), proteosome subunit ? type 9 (PSMB9), tissue inhibitor of metalloproteinase (TIMP), cyclooxygenase-2 (COX2), and IL1?, IL1?, and IL6. Each genetic polymorphism codes for a protein that has a functional role in the pathogenesis of DD.ConclusionsThere are known associations between several genetic polymorphisms and DD. Of the 20 genes analyzed, polymorphisms in vitamin D receptor, aggrecan, Type IX collagen, asporin, MMP3, IL1, and IL6 show the most promise as functional variants. Genetic studies are crucial for understanding the mechanism of the degeneration. This genetic information could eventually be used as a predictive model for determining a patient's risk for symptomatic DD.

Dataset Information

Downregulation of microRNA-125a is involved in intervertebral disc degeneration by targeting pro-apoptotic Bcl-2 antagonist killer 1.

Publications

Downregulation of microRNA-125a is involved in intervertebral disc degeneration by targeting pro-apoptotic Bcl-2 antagonist killer 1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets