Identifying Key MicroRNAs Targeted by Narenmandula in a Rodent Nephropathy Model

Xiulan Wang; Chun Chang; Wenjie Jin; Arun Arun; Sudunabuqi Sudunabuqi; Aodaofu Aodaofu; Xiaowei Liu; Fengjiao Wu; Hongmei Chen

doi:10.1155/2020/9196379

Identifying Key MicroRNAs Targeted by Narenmandula in a Rodent Nephropathy Model

Evid Based Complement Alternat Med. 2020 Nov 24:2020:9196379. doi: 10.1155/2020/9196379. eCollection 2020.

Authors

Xiulan Wang¹, Chun Chang¹, Wenjie Jin¹, Arun Arun¹, Sudunabuqi Sudunabuqi¹, Aodaofu Aodaofu², Xiaowei Liu², Fengjiao Wu¹, Hongmei Chen²

Affiliations

¹ Mongolia Medical Department of Inner Mongolia University for the Nationalities, Inner Mongolia Autonomous of China, Tongliao 028000, China.
² Affiliated Hospital of Inner Mongolia University for the Nationalities, Inner Mongolia Autonomous of China, Tongliao 028000, China.

Abstract

Background: Untreated nephropathy can progress to renal failure. The traditional Mongolian remedy Narenmandula regulates the kidney "yang." This study aimed to identify key microRNAs (miRNAs) targeted by Narenmandula in a rat model of nephropathy.

Methods: Fifteen rats exhibiting normal renal function were randomized to three study arms. Nephropathy was induced in n = 10 rats using doxorubicin hydrochloride, followed by either Narenmandula treatment (treatment group) or no treatment (control group). In n = 5 rats, no doxorubicin was given and renal function remained unchanged (healthy group). Microarray analysis identified miRNAs which were differentially expressed (DE-miRNAs) between groups. Target genes of DE-miRNAs were predicted using miRWalk version 2.0, followed by enrichment analysis using DAVID, and construction of the miRNA coregulatory network using Cytoscape.

Results: Nephropathy was successfully induced, with doxorubicin resulting in differential expression of 3645 miRNAs (1324 upregulated and 2321 downregulated). Narenmandula treatment induced differential expression of a total of 159 miRNAs (102 upregulated and 57 downregulated). Upregulated DE-miRNAs (e.g., miR-497-5p, miR-195-5p, miR-181a-5p, miR-181c-5p, and miR-30e-5p) and downregulated DE-miRNAs (e.g., miR-330-3p and miR-214-3p) regulated a high number of target genes. Moreover, the miRNA pairs (e.g., miR-195-5p-miR-497-5p, miR-181a-5p-miR-181c-5p, and miR-30e-5p-miR-30a-5p) coregulated a high number of genes. Enrichment analysis indicated functional synergy between miR-30e-5p-miR-30a-3p, miR-34a-5p-miR-30e-5p, miR-30e-5p-miR-195-3p, and miR-30a-3p-miR-195-3p pairs.

Conclusion: Narenmandula may modulate doxorubicin-induced nephropathy via targeting miR-497-5p, miR-195-5p, miR-181a-5p, miR-181c-5p, miR-30e-5p, miR-330-3p, miR-214-3p, miR-34a-5p, miR-30a-3p, and miR-30a-5p.