Related Experiment Video
Updated: Feb 9, 2026
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
MiR-199a-3p affects the multi-chemoresistance of osteosarcoma through targeting AK4
Wang Lei1, Chen Yan1, Jiang Ya1
1Department of orthopaedic surgery, the third people's hospital of Hefei, Hefei, 230031, Anhui, China.
Background:
MicroRNAs (miRNAs) play vital roles in regulating various biological processes. The dysregulations of miRNAs may result in severe human diseases, including cancer.
Methods:
We performed the qRT-PCR, western blot and the luciferase reporter assays to test whether Adenylate Kinase 4 (AK4) is the target of miR-199a-3p. Up- or down-regulation of miR-199a-3p and/or the AK4 gene was done to detect their roles in OS multi-drug resistance using drug resistance profiling assays. We further predicted the putative signal pathway involved in the miR-199a-3p-mediated OS drug-resistance.
Results:
The AK4 gene is one of the targets of miR-199a-3p and negatively correlates with the effect of miR-199a-3p on OS drug-resistance. In addition, the activity of the NF-кB signaling pathway was drastically altered by the forced changes of the miR-199a-3p level in OS cells.
Conclusions:
Our data revealed that both miR-199a-3p and its target gene AK4 are reversely correlated with the OS drug resistance.
Insights
MicroRNAs (miRNAs) regulate biological processes, and their dysregulation is linked to cancer. This study found that miR-199a-3p targets AK4, and both are inversely related to osteosarcoma drug resistance.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- MicroRNAs (miRNAs) are crucial regulators of biological processes.
- Dysregulation of miRNAs is implicated in various human diseases, including cancer.
Purpose of the Study:
- To investigate the role of miR-199a-3p and its target gene, Adenylate Kinase 4 (AK4), in osteosarcoma (OS) multi-drug resistance.
- To elucidate the signaling pathway involved in miR-199a-3p-mediated OS drug resistance.
Main Methods:
- Quantitative reverse transcription-polymerase chain reaction (qRT-PCR)
- Western blot analysis
- Luciferase reporter assays
- Drug resistance profiling assays
- Gene expression manipulation (up/down-regulation)
Main Results:
- Adenylate Kinase 4 (AK4) was identified as a direct target of miR-199a-3p.
- AK4 expression was found to be inversely correlated with the efficacy of miR-199a-3p in overcoming OS drug resistance.
- The activity of the NF-κB signaling pathway was significantly modulated by altering miR-199a-3p levels in OS cells.
Conclusions:
- Both miR-199a-3p and its target gene AK4 exhibit an inverse correlation with osteosarcoma drug resistance.
- These findings suggest a potential therapeutic strategy targeting the miR-199a-3p/AK4 axis to enhance chemo-sensitivity in osteosarcoma.
Related Concept Videos
01:22Multi-input and Multi-variable systems
In the absence of...
02:31Multi-Step Reactions
02:51Multi-species Conserved Sequences
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:26Targets for Drug Action: Overview
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
01:29Insertion of Multi-pass Transmembrane Proteins in the RER
The multipass transmembrane proteins are the type IV integral membrane proteins with multiple topogenic sequences determining their spatial arrangement in the ER membrane. Nearly all multipass proteins lack a cleavable signal sequence and use...