Correlation Between Serum miR-154-5p and Osteocalcin in Males and Postmenopausal Females of Type 2 Diabetes With Different Urinary Albumin Creatinine Ratios

Abstract

Purpose: To investigate the serum levels of miR-154-5p, osteocalcin (OC), and other clinical parameters in male and post-menopausal female type 2 diabetes mellitus (T2DM) patients with different urinary albumin creatinine ratio (UACR) levels and to discuss the relationship between miR-154-5p and glycolipid metabolism, bone metabolism, and different urinary albumin excretion rate in T2DM. Methods: Seven hundred thirty-eight T2DM patients were categorized into six groups, including 374 men and 364 post-menopausal women who were sub-divided into three groups based on albumin excretion that involved normal albuminuria, microalbuminuria, and large amount of albuminuria (138, 127, 109, 135, 125, and 104 cases, UACR<30, 30–300, and >300 mg/g, M1, M2, M3, F1, F2, and F3). Measurement of circulating miR-154-5p, OC, and other biochemical indicators were performed by real-time PCR, ELISA, and chemiluminescence assays in T2DM patients and in 141 M0 and 139 F0 control subjects. Results: There are few differences appeared between groups. Comparing with men, women had higher age, waist-to-hip ratio (WHR), adiponectin (ADPN), connective tissue growth factor (CTGF), UACR, procollagen type 1 N-terminal propeptide (P1NP), β-C-terminal telopeptide of type I collagen (β-CTx), OC, and miR-154-5p, but lower FPG, HOMA-IR, and HbA1c. T2DM patients with albuminuria (micro or macro) had lower bone turnover markers (P1NP, β-CTx, and OC) and adiponectin, but higher HbA1c, CTGF, and miR-154-5p. In addition, after regression analysis, UACR was positively correlated with CTGF, HbA1c, and miR-154-5p, and negatively correlated with ADPN and bone turnover markers (P1NP, β-CTx, and OC). However, OC showed a positive correlation with ADPN and other bone turnover markers (P1NP and β-CTx), but negative correlation with CTGF, UACR, and miR-154-5p in all three groups. Conclusion: These findings suggested that increased serum levels of miR-154-5p and decreased OC levels may influence osteogenesis and proteinuria in T2DM and may identify novel targets for diagnosis and treatment of diabetic kidney disease and osteoporosis.

miR-154-5p Affects the TGFβ1/Smad3 Pathway on the Fibrosis of Diabetic Kidney Disease via Binding E3 Ubiquitin Ligase Smurf1

“…The TGFβ1/ Smads pathway is a classic DKD way to regulate the proliferation and fibrosis of mesangial cells [6,7]. MicroRNA (miRNA) is a kind of noncoding RNA with the length of 18-25 highly conserved nucleic acids of which miR-154 is located in the miRNA-rich region of the 14q32 singlestranded chromosome in mammals [8], with one of the mature, miR-154-5p, indicating significant correlation with urine protein and fibrotic factors of diabetic patients in our previous studies [9,10]. However, the specific mechanism of miR-154-5p regulating DKD has not been studied.…”

“…Studies have shown that multiple families of miRNA clusters are involved in the pathogenesis of DKD, such as let-7 family, miR-21, and miR-377, which are involved in the proliferation and apoptosis of mesangial cells under the condition of high glucose, while miR-34a-5p, miR-184, and miR-1915-5p are associated with renal tubulointerstitial fibrosis [30,31]. Our previous studies found that compared with the normal control group, serum miR-154-5p expression in type 2 diabetic patients was significantly increased and positively correlated with UACR, HbA1c, and fibrosis factors (CTGF, VEGF, FN and TGFβ1) [9,10], indicating that human circulating miR-154-5p was closely related to renal fibrosis. This is the first time that miR-154-5p has been found to be associated with DKD fibrosis so far, suggesting that miR-154-5p in circulating blood may be potentially associated with blood glucose and proteinuria regulating the process of DKD glomerular fibrosis.…”

MicroRNA-154-5p regulates the HPV16 E7-pRb pathway in Cervical Carcinogenesis by targeting CUL2

“…Our findings indicate that CUL2 is a downstream target of miR-154-5p. miR-154-5p is located on human chromosome 14q32 and is involved in the pathophysiology of various disorders [23]. Recently it has been shown that miR-154-5p, which is involved as a suppressor in the regulation of cancers, was downregulated in breast cancer, colorectal cancer, glioma, hepatocellular cancer, osteosarcoma, nasopharyngeal carcinoma, and non-small cell lung cancer [24][25][26][27][28][29][30][31].…”

<p>MicroRNA-154: A Novel Candidate for Diagnosis and Therapy of Human Cancers</p>

“…host gene 5 (SNHG5) is upstream regulator of miR-154-5p. 15 Today, miR-154 is a hotspot and its roles have already been tightly investigated in numerous physiological and pathological processes such as diabetes, 16 spermatogenesis, 17 endometritis 18 and cardiac complications. 19 Currently, there is no miR-154-based treatment, however, in a clinical trial (ChiCTR1800019872), Ren et al, tried to investigate diagnostic potential of miR-154-5p in patients with type 2 diabetes mellitus.…”