Evidence map›Paper›PMID 34430428›Full record

ArticleTranslational pediatrics2021

AKT3 and related molecules as potential biomarkers responsible for cryptorchidism and cryptorchidism-induced azoospermia.

Hongshuai Jia, Tiantian Ma, Shujing Jia, Yuru Ouyang

Registry-linked trialOpen access · diamondAbstract read
In one paragraph

Article in Translational pediatrics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07315737 (miRNAs Associated With Undescended and Retractile Testes), which is not on this map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
5.8field-weighted citation impact, top 3% of its field
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.

NCT07315737 completednot on this mapstarted 2022, after this paper: background citation

miRNAs Associated With Undescended and Retractile Testes

TypeobservationalSponsorDr. Mevlüt KeleşRan2022 to 2023Enrolled28ConditionsMIRAS, Testicular Abnominalies, Undescended TestesArmsmiRNA
3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 29 citations in OpenAlex.

  1. Observational
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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

4 authors at 4 institutions in 1 country.

Hongshuai JiaDepartment of Urology, Capital Institute of Pediatrics, Beijing, China.
Tiantian MaDepartment of Nephrology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
Shujing JiaCentral Laboratory, the First Hospital of Handan, Handan, China.
Yuru OuyangDepartment of Urology, Capital Institute of Pediatrics, Beijing, China.
Capital Institute of Pediatrics · CNHandan College · CNPeking Union Medical College Hospital · CNTianjin Children's Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCryptorchidism is a common congenital malformation strongly related to future oligospermia and male infertility. Normally functioning early-stage spermatogonia are vital to ensure fertility. The present study aimed to identify new differentially expressed genes (DEGs) associated with signaling pathways related to spermatogonial stem cell (SSC) maintenance during early spermatogenesis.

methodsGEO2R was used to screen for genes differentially regulated in cryptorchidism using mRNA expression profiling data in the GEO database. DAVID was used to perform GO and KEGG enrichment analysis of DEGs to analyze their functions. A protein-protein interaction (PPI) network of DEGs was constructed using the STRING database. The hub genes in the PPI networks were identified using Maximal Clique Centrality (MCC) in Cytohubba, and the top 50 genes were displayed as hub genes using Cytoscape software. Then, the miRNAs targeting hub genes were predicted using miRWalk and an mRNA-miRNA interaction network was constructed using Cytoscape. We took the intersection of these target miRNAs and the differentially expressed miRNAs identified from a non-coding RNA sequencing dataset, GSE149084. Furthermore, the intersected miRNAs and their predicted target genes were validated in the testicular tissue of rats with cryptorchidism.

resultsA total of 474 DEGs were identified, most of which were annotated to the PI3K-AKT-mTOR signaling pathway. Hub genes related to the pathway were predicted to be targeted by 27 miRNAs. Further miRNA mining revealed that miRNA-7-5p and miRNA-519d-3p were both dysregulated in cryptorchidism patients. Further, we found that these two miRNAs were predicted with high confidence to share a common target gene, AKT3. In the testicular tissue of rats with cryptorchidism, miRNA-519d-3p was upregulated while miRNA-7-5p and AKT3 were downregulated. We also found that AKT3 plays an essential role in regulating SSC state through the PI3K-AKT-mTOR signaling pathway and that AKT3 is one of the key genes related to SSC self-renewal, proliferation, and differentiation.

conclusionsThe PI3K-AKT-mTOR signaling pathway functions in SSC maintenance, and alterations in this pathway may explain defects in spermatogenesis. AKT3-related miRNAs, including hsa-miR-7-5p and hsa-miR-519d-3p, might be responsible for cryptorchidism and cryptorchidism-induced azoospermia and serve as potential biomarkers.

Indexed as

azoospermiabioinformatic analysisbiomarkersCryptorchidismmiRNA

Identifiers

PMID34430428
PMCPMC8349953
OpenAlexW3180114688

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Registered trials

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.