Serum miR-195-5p Exhibits Clinical Significance in the Diagnosis of Essential Hypertension with Type 2 Diabetes Mellitus by Targeting DRD1.

OBJECTIVES: Diagnosis and management of essential hypertension (EH) or type 2 diabetes mellitus (T2DM) by combining comprehensive treatment and classificatory diagnosis have been continuously improved. However, understanding the pathogenesis of EH patients with concomitant T2DM and subsequent treatment remain the major challenges owing to the lack of non-invasive biomarkers and information regarding the underlying mechanisms. METHODS: Herein, we collected 200 serum samples from EH and/or T2DM patients and healthy donors (N). Gene-expression profiling was conducted to identify candidate microRNAs with clinical significance. Then, a larger cohort of the aforementioned patients and 50 N were used to identify the correlation between the tumor suppressor miR-195-5p and EH and/or T2DM. The dual-luciferase reporter assay was used to explore the target genes of miR-195-5p. The suppressive effects of miR-195-5p on the 3'-UTR of the dopamine receptor D1 (DRD1) transcript in EH patients with concomitant T2DM were verified as well. RESULTS: Compared with that in other groups, serum miR-195-5p was highly downregulated in EH patients with concomitant T2DM. miR-195-5p overexpression efficiently suppressed DRD1 expression by binding to the two 3'-UTRs. Additionally, two single nucleotide polymorphisms, including 231T-A and 233C-G, in the miR-195-5p binding sites of the DRD1 3'-UTR were further identified. Collectively, we identified the potential clinical significance of DRD1 regulation by miR-195-5p in EH patients with concomitant T2DM. CONCLUSIONS: Our data suggested that miR-195-5p circulating in the peripheral blood served as a novel biomarker and therapeutic target for EH and T2DM, which could eventually help address major challenges during the diagnosis and treatment of EH and T2DM.

Serum mir-195-5p exhibits clinical significance in the diagnosis of essential hypertension with type 2 diabetes

OBJECTIVES: Diagnosis and management of essential hypertension (EH) or type 2 diabetes mellitus (T2DM) by combining comprehensive treatment and classificatory diagnosis have been continuously improved. However, understanding the pathogenesis of EH patients with concomitant T2DM and subsequent treatment remain the major challenges owing to the lack of non-invasive biomarkers and information regarding the underlying mechanisms. METHODS: Herein, we collected 200 serum samples from EH and/or T2DM patients and healthy donors (N). Gene-expression profiling was conducted to identify candidate microRNAs with clinical significance. Then, a larger cohort of the aforementioned patients and 50 N were used to identify the correlation between the tumor suppressor miR-195-5p and EH and/or T2DM. The dual-luciferase reporter assay was used to explore the target genes of miR-195-5p. The suppressive effects of miR-195-5p on the 3′-UTR of the dopamine receptor D1 (DRD1) transcript in EH patients with concomitant T2DM were verified as well. RESULTS: Compared with that in other groups, serum miR-195-5p was highly downregulated in EH patients with concomitant T2DM. miR-195-5p overexpression efficiently suppressed DRD1 expression by binding to the two 3′-UTRs. Additionally, two single nucleotide polymorphisms, including 231T-A and 233C-G, in the miR-195-5p binding sites of the DRD1 3′-UTR were further identified. Collectively, we identified the potential clinical significance of DRD1 regulation by miR-195-5p in EH patients with concomitant T2DM. CONCLUSIONS: Our data suggested that miR-195-5p circulating in the peripheral blood served as a novel biomarker and therapeutic target for EH and T2DM, which could eventually help address major challenges during the diagnosis and treatment of EH and T2DM.

Long non­coding RNA RP11­400N13.3 promotes the progression of colorectal cancer by regulating the miR­4722­3p/P2RY8 axis.

Accumulating evidence has shown that long non­coding RNAs (lncRNAs) play significant roles in the development and progression of many types of cancer including colorectal cancer. RP11­400N13.3 is a novel lncRNA discovered recently and its biological function and underlying mechanism in colorectal cancer remain elusive. This study aimed to reveal the relationship between RP11­400N13.3 and colorectal cancer. Our results demonstrated that the expression of RP11­400N13.3 was significantly upregulated in both colorectal cancer tissues and cell lines as compared to normal adjacent tissues and normal colonic epithelial cells by RT­qPCR, respectively. Upregulation of RP11­400N13.3 was found to be correlated with a poor overall survival rate. Functional studies revealed that RP11­400N13.3 facilitated the proliferation, migration, invasion and tumor growth of colorectal cancer cells while inhibiting the apoptosis of cancer cells in vitro and in vivo. We also observed that RP11­400N13.3 serves as a sponge for miR­4722­3p, and that P2Y receptor family member 8 (P2RY8) was predicted to be a target of miR­4722­3p by bioinformatics analysis. Western blot assay indicated that the expression of P2RY8 was negatively or positively regulated by miR­4722­3p or RP11­400N13.3. In addition, rescue experiments revealed that RP11­400N13.3 promoted proliferation, migration and invasion by directly regulating the expression of miR­4722­3p and P2RY8. In conclusion, our results revealed that RP11­400N13.3 promoted colorectal cancer progression via modulating the miR­4722­3p/P2RY8 axis, thus suggesting RP11­400N13.3 as a potential therapeutic target for the treatment of colorectal cancer.

LncPRYP4-3 serves as a novel diagnostic biomarker for dissecting subtypes of metabolic associated fatty liver disease by targeting RPS4Y2.

Longitudinal studies have improved current diagnostics and management of metabolic associated fatty liver disease (MAFLD) patients by liver biopsy and therapeutic intervention, yet the deficiency of biomarker spectrum for dissecting subtypes largely hinders the symptomatic treatment. We originally enriched serum from peripheral blood of 618 healthy donors (HD) and 580 MAFLD (400 NAFL, 180 NASH) patients according to multiple clinicopathological indicators. Microarray profiling and qRT-PCR were conducted to identify lncRNAs as candidate biomarkers of MAFLD. Then, we analyzed the matching score of the indicated lncRNA with CAP or MAFLD-associated pathological parameters as well. Additionally, we took advantage of interaction network together with gene expression profiling analysis to further explore the underlying target genes of the identified lncRNA. Herein, we found CAP in nearly all of the NAFL (399/400) and NASH (179/180) patients was higher than that in the HDs (611/618). The differentially expressed lncRNAs were involved in multiple metabolic or immunologic processes by regulating MAFLD-associated pathways. Of them, serum lncPRYP4-3 was identified as a novel candidate biomarker of MAFLD, which was further confirmed by correlation analysis with clinical indicators. Thereafter, we deduced PRS4Y2 was a candidate target of lncPRYP4-3 and mediated the dysfunction in NAFL and NASH patients. Serum lncPRYP4-3 served as a novel biomarker of MAFLD and helped distinguish the subtypes and benefit precise intervention therapy. Our findings also provided overwhelming new evidence for the alteration in biological processes and gene ontology in MAFLD patients.