---
title: "SNHG12 promotes diabetic nephropathy via the miR-129-5p / IL6ST regulatory axis"
id: "pubmed-42579189"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42579189"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42579189/"
doi: "10.1007/s11033-026-12547-7"
published_at: "2026-08-11T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# SNHG12 promotes diabetic nephropathy via the miR-129-5p / IL6ST regulatory axis
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42579189
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42579189/)
- **DOI:** [10.1007/s11033-026-12547-7](https://doi.org/10.1007%2Fs11033-026-12547-7)
- **Published At:** 2026-08-11T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This study investigated the role of the long non-coding RNA **SNHG12** in the pathogenesis of **diabetic nephropathy (DN)** using clinical samples and an in vitro high-glucose HK-2 cell model. - The clinical cohort included 150 patients with type 2 diabetes mellitus (T2DM) and 150 patients with DN; expression of SNHG12, **miR-129-5p**, and **IL6ST** was measured by RT-qPCR. - In DN patients, SNHG12 and **IL6ST** expression were significantly increased, while **miR-129-5p** was downregulated; multivariate regression identified SNHG12 as a risk factor for DN. - In HK-2 cells exposed to **high glucose (HG)**, SNHG12 knockdown increased cell proliferation, decreased apoptosis, reduced inflammatory cytokine production by ELISA, and lowered fibrosis markers (TGF-β1 and α-SMA). - Mechanistic assays (RIP and dual-luciferase reporter) demonstrated that SNHG12 can directly bind and sponge **miR-129-5p**, and miR-129-5p targets the 3'UTR of **IL6ST**. - Functional rescue experiments showed that inhibition of **miR-129-5p** or overexpression of **IL6ST** partially reversed the protective effects of SNHG12 silencing on cell proliferation, apoptosis, inflammation, and fibrosis markers. - The authors conclude that SNHG12 promotes DN progression by upregulating **IL6ST** through sponging of **miR-129-5p**, and that SNHG12 may have potential as an auxiliary diagnostic biomarker for DN. - The study received ethics approval from the listed institutional committee and all participants gave written informed consent; the authors declared no competing interests.
## Clinical Analysis & Structured Key Points
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XianyuxinQDU@163.com.") Affiliations Expand ### Affiliations * 1 Department of Endocrinology, Qingdao Municipal Hospital, Qingdao, 266000, China. * 2 Department of Nephrology, Tongji Medical College, Traditional Chinese and Western Medicine Hospital of Wuhan, Huazhong University of Science and Technology, Wuhan, 430022, China. * 3 Renmin Hospital of Wuhan University, Hubei General Hospital, Wuhan, 430060, China. * 4 Department of Endocrinology, Tongji Medical College, The Central Hospital of Wuhan, Huazhong University of Science and Technology, Wuhan, 430014, China. * 5 Department of Endocrinology, The Affiliated Hospital of Qingdao University, No. 59, Haier Road, Qingdao, 266000, Shandong, China. XianyuxinQDU@163.com. * PMID: **42579189** * DOI: [ 10.1007/s11033-026-12547-7 ](https://doi.org/10.1007/s11033-026-12547-7) Item in Clipboard # LncRNASNHG12 regulates the development of diabetic nephropathy through miR-129-5p/IL6ST axis Liping Dong et al. Mol Biol Rep. 2026. Show details Display options Display options Format Abstract PubMed PMID Mol Biol Rep Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Mol+Biol+Rep%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Mol+Biol+Rep%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42579189/) . 2026 Aug 11;53(1):1381. doi: 10.1007/s11033-026-12547-7. ### Authors [Liping Dong](https://pubmed.ncbi.nlm.nih.gov/?term=Dong+L&cauthor_id=42579189)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42579189/#short-view-affiliation-1 "Department of Endocrinology, Qingdao Municipal Hospital, Qingdao, 266000, China."), [Pengcheng Sun](https://pubmed.ncbi.nlm.nih.gov/?term=Sun+P&cauthor_id=42579189)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42579189/#short-view-affiliation-2 "Department of Nephrology, Tongji Medical College, Traditional Chinese and Western Medicine Hospital of Wuhan, Huazhong University of Science and Technology, Wuhan, 430022, China."), [Yutong Hu](https://pubmed.ncbi.nlm.nih.gov/?term=Hu+Y&cauthor_id=42579189)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42579189/#short-view-affiliation-3 "Renmin Hospital of Wuhan University, Hubei General Hospital, Wuhan, 430060, China."), [Zihui Xu](https://pubmed.ncbi.nlm.nih.gov/?term=Xu+Z&cauthor_id=42579189)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42579189/#short-view-affiliation-4 "Department of Endocrinology, Tongji Medical College, The Central Hospital of Wuhan, Huazhong University of Science and Technology, Wuhan, 430014, China."), [Fei Xiong](https://pubmed.ncbi.nlm.nih.gov/?term=Xiong+F&cauthor_id=42579189)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42579189/#short-view-affiliation-2 "Department of Nephrology, Tongji Medical College, Traditional Chinese and Western Medicine Hospital of Wuhan, Huazhong University of Science and Technology, Wuhan, 430022, China."), [Yuxin Xian](https://pubmed.ncbi.nlm.nih.gov/?term=Xian+Y&cauthor_id=42579189)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42579189/#short-view-affiliation-5 "Department of Endocrinology, The Affiliated Hospital of Qingdao University, No. 59, Haier Road, Qingdao, 266000, Shandong, China. XianyuxinQDU@163.com.") ### Affiliations * 1 Department of Endocrinology, Qingdao Municipal Hospital, Qingdao, 266000, China. * 2 Department of Nephrology, Tongji Medical College, Traditional Chinese and Western Medicine Hospital of Wuhan, Huazhong University of Science and Technology, Wuhan, 430022, China. * 3 Renmin Hospital of Wuhan University, Hubei General Hospital, Wuhan, 430060, China. * 4 Department of Endocrinology, Tongji Medical College, The Central Hospital of Wuhan, Huazhong University of Science and Technology, Wuhan, 430014, China. * 5 Department of Endocrinology, The Affiliated Hospital of Qingdao University, No. 59, Haier Road, Qingdao, 266000, Shandong, China. XianyuxinQDU@163.com. * PMID: **42579189** * DOI: [ 10.1007/s11033-026-12547-7 ](https://doi.org/10.1007/s11033-026-12547-7) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background:** Diabetic Nephropathy (DN) pathogenesis remains incompletely understood. **Objectives:** This study aimed to explore the mechanistic function of long non-coding RNA (lncRNA) SNHG12 in the progression of DN. **Materials and methods:** In this study, 150 type 2 diabetes mellitus (T2DM) patients and 150 DN patients were recruited. Human kidney-2 (HK-2) cells were exposed to high glucose (HG) to establish a DN cell model. The target gene expression was assessed by reverse transcription quantitative real-time PCR (RT-qPCR), cell proliferation was evaluated using the Cell Counting Kit-8 (CCK-8) assay, cell apoptosis was determined by flow cytometry, inflammatory factor levels were measured by enzyme-linked immunosorbent assay (ELISA), and molecular interactions were confirmed through the RNA immunoprecipitation (RIP) and dual-luciferase reporter assay. **Results:** In DN patients, SNHG12 and interleukin 6 signal transducer (IL6ST) were significantly elevated, whereas miR-129-5p expression was down-regulated, indicating that SNHG12 may serve as a potential biomarker for the auxiliary diagnosis of DN. Multivariate regression analysis showed that SNHG12 was a risk factor for DN. Moreover, under HG conditions, silencing of SNHG12 promoted cell proliferation, inhibited apoptosis, and mitigated inflammatory responses, as well as attenuated fibrosis, reflected by decreased expression of transforming growth factor-beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA). Furthermore, SNHG12 could directly bind to and regulate miR-129-5p, which in turn targeted the 3'UTR of IL6ST. Inhibition of miR-129-5p or overexpression of IL6ST partially reversed the protective effects of SNHG12 knockdown on cellular functions. **Conclusion:** SNHG12 promoted the progression of DN by upregulating IL6ST expression through the sponging of miR-129-5p. **Keywords:** Diabetic nephropathy; IL6ST; SNHG12; miR-129-5p. © 2026. The Author(s), under exclusive licence to Springer Nature B.V. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of Traditional Chinese and Western Medicine Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, and all participants provided written informed consent. The procedures used in this study adhere to the tenets of the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. ## References 1. 1. Chen W, Zhang M, Guo Y, Wang Z, Liu Q, Yan R, Wang Y, Wu Q, Yuan K, Sun W (2021) The Profile and Function of Gut Microbiota in Diabetic Nephropathy. Diabetes metabolic syndrome obesity: targets therapy 14:4283–4296. - [DOI](https://doi.org/10.2147/dmso.s320169) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/34703261/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/8541750/) 2. 1. Kovacevic S, Zdravkovic V, Blagojevic J, Djordjevic S, Miolski J, Gasic V, Jelovac M, Ugrin M, Pavlovic S, Jesic M (2024) Association of variants in AGTR1, ACE, MTHFR genes with microalbuminuria and risk factors for the onset of diabetic nephropathy in adolescents with type 1 diabetes in the population of Serbia. PLoS ONE 19(10):e0312489. - [DOI](https://doi.org/10.1371/journal.pone.0312489) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/39446857/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/11500908/) 3. 1. Deng J, Zheng C, Hua Z, Ci H, Wang G, Chen L (2022) Diosmin mitigates high glucose-induced endoplasmic reticulum stress through PI3K/AKT pathway in HK-2 cells. BMC Complement Med Ther 22(1):116. - [DOI](https://doi.org/10.1186/s12906-022-03597-y) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/35477428/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/9044681/) 4. 1. Liu Y, Cui X, Zhang X, Xie Z, Wang W, Xi J, Xie Y (2023) Exploring the potential mechanisms of Tongmai Jiangtang capsules in treating diabetic nephropathy through multi-dimensional data. Front Endocrinol 14:1172226. - [DOI](https://doi.org/10.3389/fendo.2023.1172226) 5. 1. Zhang C, Fang Y, Lin Z, Zhuo Y, Wan J, Zhang X (2025) Association between physiological serum total bilirubin concentrations and the progression of diabetic nephropathy. Front Endocrinol 16:1588568. - [DOI](https://doi.org/10.3389/fendo.2025.1588568) Show all 36 references ## MeSH terms * Apoptosis / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Apoptosis%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Apoptosis) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42579189/) * Cell Line Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cell+Line%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Cell+Line) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42579189/) * Cell Proliferation / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cell+Proliferation%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Cell+Proliferation) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42579189/) * Cytokine Receptor gp130* / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cytokine+Receptor+gp130%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Cytokine+Receptor+gp130) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42579189/) * Cytokine Receptor gp130* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cytokine+Receptor+gp130%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Cytokine+Receptor+gp130) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42579189/) * Diabetes Mellitus, Type 2 / complications Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Diabetes+Mellitus%2C+Type+2%2Fcomplications%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Diabetes+Mellitus%2C+Type+2) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42579189/) * Diabetes Mellitus, Type 2 / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Diabetes+Mellitus%2C+Type+2%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Diabetes+Mellitus%2C+Type+2) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42579189/) * Diabetes Mellitus, Type 2 / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Diabetes+Mellitus%2C+Type+2%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Diabetes+Mellitus%2C+Type+2) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42579189/) * Diabetic Nephropathies* / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Diabetic+Nephropathies%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Diabetic+Nephropathies) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42579189/) * Diabetic Nephropathies* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Diabetic+Nephropathies%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Diabetic+Nephropathies) * [ Add to
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