Regulation of the Low-Density Lipoprotein Receptor-Related Protein LRP6 and Its Association With Disease: Wnt/β-Catenin Signaling and Beyond

Jeong, Wonyoung; Jho, Eek-hoon

doi:10.3389/fcell.2021.714330

Cited by 33 publications

(19 citation statements)

References 142 publications

(190 reference statements)

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“…It has been well known that mutation or dysregulation of LRP6 proteins is directly associated with oxidative stress, dyslipidemia, atherosclerosis, and coronary artery disease [ 19 – 21 ]. Caspase-3 activities were enormously increased in 18-hour H/R-exposed HUVECs but remarkably reduced after transfection with mimic-126.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of miR-126 Protects Hypoxic-Reoxygenation-Exposed HUVEC Cellular Injury through Regulating LRP6 Expression

Sheikh

Almaeen

Alduraywish

et al. 2022

Oxidative Medicine and Cellular Longevity

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The aim of the study was to explore the clinical impact of circulatory miR-126 as a candidate for novel biomarker in patients with coronary artery disease (CAD) and its protective role against hypoxia/reoxygenation- (H/R-) exposed HUVEC cellular injury. A total of 278 subjects, which included 153 subjects with angiographically confirmed CAD, 70 unstable angina subjects, and 55 healthy individuals, along with 18-hour HR-induced HUVECs were recruited in this study. Plasma miR-126 levels were significantly downregulated in stable and unstable CAD patients as well as 18-hour HR-exposed HUVECs as compared with controls. Stable and unstable CAD subjects were significantly differentiated from healthy individuals with a predictive value of AUC 0.903 and 0.923, respectively. Moreover, peripheral circulatory miR-126 expressions in elderly (71-90 years) stable and unstable CAD patients were comparatively lower than younger (30-50 years) subjects. The caspase-3 activity, intracellular ROS concentrations, and cellular viabilities were evidently increased in 18-hour HR-exposed HUVECs than in normal cells ( P < 0.001 ). On the contrary, mimic expressions of miR-126 prominently reduced caspase-3 activity and intracellular ROS levels and markedly enhanced HUVEC cellular viabilities ( P < 0.001 ). LRP6 expressions were significantly elevated in HR-induced HUVECs, whereas overexpression of miR-126 remarkably decreased LRP6 expressions ( P < 0.001 ). Plasma miR-126 could be used as a novel biomarker for early prediction of CAD subjects. Overexpression of miR-126 significantly improved HUVEC cellular viabilities by downregulation of LRP6 protein expression, suggesting a potential therapeutic target for CAD patients.

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Section: Discussionmentioning

confidence: 99%

Overexpression of miR-126 Protects Hypoxic-Reoxygenation-Exposed HUVEC Cellular Injury through Regulating LRP6 Expression

Sheikh

Almaeen

Alduraywish

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…On the other hand, it is well established that LRP6 regulates breast cancer. LRP6’s expression is most often up-regulated in breast cancer tissue, and overexpression or knockdown of LRP6 causes or halts breast tumorigenesis ( 135 ). In line with the study conducted in RB, the expression of LRP6 in the form of a ceRNA axis also experiences an increase in expression, and in the direction of RB development, this increase in expression demonstrates its oncogenic effects ( 30 , 33 ).…”

Section: Discussionmentioning

confidence: 99%

CircRNA-Associated CeRNAs Regulatory Axes in Retinoblastoma: A Systematic Scoping Review

et al. 2022

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Retinoblastoma (RB) is one of the most common childhood cancers caused by RB gene mutations (tumor suppressor gene in various patients). A better understanding of molecular pathways and the development of new diagnostic approaches may lead to better treatment for RB patients. The number of studies on ceRNA axes is increasing, emphasizing the significance of these axes in RB. Circular RNAs (circRNAs) play a vital role in competing endogenous RNA (ceRNA) regulatory axes by sponging microRNAs and regulating gene expression. Because of the broadness of ceRNA interaction networks, they may assist in investigating treatment targets in RB. This study conducted a systematic scoping review to evaluate verified loops of ceRNA in RB, focusing on the ceRNA axis and its relationship to circRNAs. This scoping review was carried out using a six-step strategy and the Prisma guideline, and it involved systematically searching the publications of seven databases. Out of 363 records, sixteen articles were entirely consistent with the defined inclusion criteria and were summarized in the relevant table. The majority of the studies focused on the circRNAs circ_0000527, circ_0000034, and circTET1, with approximately two-fifths of the studies focusing on a single circRNA. Understanding the many features of this regulatory structure may help elucidate RB’s unknown causative factors and provide novel molecular potential therapeutic targets and medical fields.

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“…LRP6, a member of the LDLR gene family, is a co-receptor of Wnt, and the internalization of LRP6 can lead to the inhibition of Wnt/β-catenin signaling pathway ( 30 ). In addition, in hyperlipidemia rat model hyperlipidemia could inhibit dishevelled-2 expression and its phosphorylation, thus inhibiting Wnt/β-catenin signaling pathway ( 31 ). Consistently, the present study found that a low LDL-C/Apo B ratio was an independent contributor to low bone turnover in patients with T2D.…”

Section: Discussionmentioning

confidence: 99%

The Positive Relationship Between the Low-Density Lipoprotein Cholesterol/Apoprotein B Ratio and Bone Turnover Markers in Patients With Type 2 Diabetes

Lu¹,

Liu²,

Huang³

et al. 2022

Front. Endocrinol.

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BackgroundDyslipidemia may contribute to low bone turnover in patients with type 2 diabetes (T2D) through mediating oxidative stress and atherosclerosis. The low-density lipoprotein cholesterol/apoprotein B (LDL-C/Apo B) ratio is a surrogate marker of small and density low-density lipoprotein cholesterol (sd-LDL-C), a most harmful group of LDL-Cs. The present study aimed to investigate the association between the LDL-C/Apo B ratio and bone turnover in patients with T2D.MethodsThis study was a cross-sectional study enrolled patients with T2D from January 2021 to December 2021. Each participant was assessed for lipid profiles, bone turnover markers (BTMs), lumbar spine (L1-L4) and hip dual-energy X-ray absorptiometry (DXA) scans. Osteoporosis was diagnosed as a T-score lower than or equal to -2.5 at the spine or hip.ResultsA total of 335 patients with T2D were enrolled in the study, and the LDL-C/Apo B ratio ranged from 0.78 to 4.00. Along with the LDL-C/Apo B ratio tertile ascending, osteocalcin (OC), C-terminal telopeptide (CTx) and N-terminal propeptide of type-I procollagen (PINP) levels gradually increased (all p < 0.05). There were no differences in lumbar spine and hip T-score, proportion of osteoporosis (all p > 0.05) among the three subgroups. The LDL-C/Apo B ratio was positively correlated with lnOC (r = 0.244, p < 0.001), lnCTx (r = 0.226, p < 0.01) and lnPINP (r = 0.211, p < 0.001). These significant positive correlations persisted even when divided into male and female subgroups. Furthermore, three multiple linear regression analyses were constructed to investigate the independent association of the LDL-C/Apo B ratio with the BTMs levels. After adjusting for other clinical parameters, the LDL-C/Apo B ratio was still significantly associated with OC level (β = 0.199, t = 3.348, p < 0.01), CTx level (β = 0.238, t = 4.084, p < 0.001) and PINP level (β = 0.162, t = 2.741, p < 0.01).ConclusionThe LDL-C/Apo B ratio was significantly and positively associated with BTMs in patients with T2D. In clinical practice, more attention should be paid to the patients with T2D whose LDL-C/Apo B ratio is relatively low for the purpose of maintaining bone health.

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Regulation of the Low-Density Lipoprotein Receptor-Related Protein LRP6 and Its Association With Disease: Wnt/β-Catenin Signaling and Beyond

Cited by 33 publications

References 142 publications

Overexpression of miR-126 Protects Hypoxic-Reoxygenation-Exposed HUVEC Cellular Injury through Regulating LRP6 Expression

Overexpression of miR-126 Protects Hypoxic-Reoxygenation-Exposed HUVEC Cellular Injury through Regulating LRP6 Expression

CircRNA-Associated CeRNAs Regulatory Axes in Retinoblastoma: A Systematic Scoping Review

The Positive Relationship Between the Low-Density Lipoprotein Cholesterol/Apoprotein B Ratio and Bone Turnover Markers in Patients With Type 2 Diabetes

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