Evidence map›Paper›PMID 41088271›Full record

ArticleCell communication and signaling : CCS2025

Mitochondrial ribosomal protein L12 mediates metabolic reorganization in clear cell renal cell carcinoma by regulating mitochondrial biosynthesis.

Shengnan Sun, Dun Su, Tianyi Dong, Bo Wang, Xingzhao Ji, Lingju Chu, Shicong Lu, Tianyi Zhang, Xiaoming Sun, Yi Liu and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Shengnan Sun *Shandong Provincial Key Medical and Health Laboratory of Cell Metabolism, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
Dun Su *Shandong Provincial Key Medical and Health Laboratory of Cell Metabolism, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
Tianyi Dong *Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Bo WangDepartment of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Xingzhao JiShandong Provincial Key Medical and Health Laboratory of Cell Metabolism, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
Lingju ChuShandong Provincial Key Medical and Health Laboratory of Cell Metabolism, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
Shicong LuDepartment of Oncology Intervention, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, Shandong, China.
Tianyi ZhangShandong Provincial Key Medical and Health Laboratory of Cell Metabolism, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
Xiaoming SunShandong Provincial Key Medical and Health Laboratory of Cell Metabolism, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
Yi LiuDepartment of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China. liuyishanyi@email.sdu.edu.cn.
Qiang WanShandong Provincial Key Medical and Health Laboratory of Cell Metabolism, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China. wanqiang@sdu.edu.cn.

Funding

National Natural Science Foundation of China 82370725, 82371604, 82271622, 82071569, 82070756, 82102395, 82200049 and 82101639Natural Science Foundation of Shandong Province ZR2023QH316, ZR2021QH083, ZR2021ZD35, ZR2022QH349 and ZR2022QH374
6 · The paper itself

Abstract

backgroundClear cell renal cell carcinoma (ccRCC) is characterized by mitochondrial dysfunction and the Warburg effect, which refers to enhanced aerobic glycolysis. Mitochondrial ribosomal protein 12 (MRPL12) plays a pivotal role in mitochondrial biogenesis by promoting mitochondrial transcription through its interaction with POLRMT. Our previous studies have demonstrated that MRPL12 is involved in the progression of diabetic kidney disease (DKD) and acute kidney injury (AKI). However, its specific role in ccRCC remains unclear. Therefore, this study aims to elucidate the function of MRPL12 in the metabolic reprogramming of ccRCC.

methodsOnline databases and tissue microarray analysis were utilized to explore the role of MRPL12 in ccRCC. Quantitative real-time PCR (qRT-PCR) was performed to quantify mRNA expression levels, while Western blotting, immunofluorescence (IF), and immunohistochemistry (IHC) were employed to evaluate protein expression of the relevant genes. In vitro functional assays were conducted to determine the biological effects of MRPL12, and aerobic glycolysis was assessed using Seahorse XF Analyzers to measure cellular metabolic activity. Mass spectrometry analysis, combined with Gene Ontology (GO) analysis and integrated with Ingenuity Pathway Analysis (IPA), was carried out to identify potential pathway interconnections. To investigate the regulatory mechanism, chromatin immunoprecipitation (ChIP) assays were performed to examine the binding interaction between HIF-1α and the MRPL12 promoter. Finally, an in vivo mouse model was established to further elucidate the functional role of MRPL12 in ccRCC progression.

resultsMRPL12 is significantly downregulated in ccRCC tissues, and its reduced expression is associated with poor prognosis. MRPL12 inhibits ccRCC cell proliferation, migration, and invasion by modulating mitochondrial metabolism. Overexpression of MRPL12 enhances oxidative phosphorylation (OXPHOS) and suppresses aerobic glycolysis, while MRPL12 knockdown produces the opposite effects. Potential interconnections between the MRPL12, ILK, ISGylation, and SUMO pathways have been identified. Additionally, HIF-1α was found to act as a transcriptional repressor of MRPL12.

conclusionOur study reveals that MRPL12 regulates mitochondrial metabolism to inhibit ccRCC cell proliferation, migration, and invasion, suggesting that targeting MRPL12 may represent a promising therapeutic strategy for ccRCC.

Indexed as

Carcinoma, Renal CellKidney NeoplasmsMitochondriaMitochondrial ProteinsRibosomal ProteinsAnimalsCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticGlycolysisHumansMaleMiceMice, NudeMitochondrial ProteinsRibosomal Proteins

Identifiers

PMID41088271
PMCPMC12523095

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.