miR-128-3p suppresses tumor growth and enhances chemosensitivity in tongue squamous cell carcinoma through MAP2K7 targeting.
MicroRNAs
/ genetics
Tongue Neoplasms
/ genetics
Humans
Cell Line, Tumor
Cell Proliferation
/ drug effects
Gene Expression Regulation, Neoplastic
/ drug effects
Epithelial-Mesenchymal Transition
/ genetics
Drug Resistance, Neoplasm
/ genetics
Cisplatin
/ pharmacology
Cell Movement
/ genetics
Carcinoma, Squamous Cell
/ genetics
Animals
MAP Kinase Kinase Kinases
/ metabolism
MAP Kinase Signaling System
/ drug effects
Apoptosis
/ drug effects
Mice
Cisplatin resistance
MAP2K7
Tongue cancer
miR-128-3p
microRNA
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
30 Oct 2024
30 Oct 2024
Historique:
received:
23
07
2024
accepted:
21
10
2024
medline:
31
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
epublish
Résumé
MicroRNAs (miRNAs), which are key players in cancer cell resistance to chemotherapy, notably target genes associated with drug resistance. While miRNA-128-3p is recognized for its involvement in various cancers, its specific role in tumorigenesis and cisplatin (CIS) resistance in tongue cancer remains unclear. Therefore, in the present study, we endeavoured to elucidate the significance of miR-128-3p in tongue squamous cell carcinoma (TSCC), shedding light on its intricate functions and underlying mechanisms. We quantified the expression of miR-128-3p and its target genes using qRT-PCR, followed by a series of functional assays in vitro, such as proliferation and migration assays, flow cytometry analysis, and western blotting to unravel the mechanisms underlying the functions of miR-128-3p. Additionally, we validated the ability of miR-128-3p to target MAP2K7 genes through luciferase reporter assays. We observed that increased expression of miR-128-3p significantly inhibited TSCC cell migration, proliferation, and epithelial-mesenchymal transition (EMT), possibly by regulating MAP2K7 in the JNK/MAP kinase pathway through miRNA target binding. Furthermore, we showed that increased miR-128-3p levels enhanced the sensitivity of TSCC cells to CIS through the JNK/c-Jun cascade. We observed that miR-128-3p reduces the expression of c-Jun and ABC transporter genes by targeting MAP2K7, affecting JNK1/2. This inhibition possibly decreases drug efflux and thus enhances the TSCC sensitivity to CIS treatment. Our findings demonstrate oncosuppressive behaviour of miR-128-3p, which also potentially enhances the sensitivity of TSCC cells to CIS by suppressing MAP2K7 and JNK1/2, leading to evasion of apoptosis.
Sections du résumé
BACKGROUND
BACKGROUND
MicroRNAs (miRNAs), which are key players in cancer cell resistance to chemotherapy, notably target genes associated with drug resistance. While miRNA-128-3p is recognized for its involvement in various cancers, its specific role in tumorigenesis and cisplatin (CIS) resistance in tongue cancer remains unclear. Therefore, in the present study, we endeavoured to elucidate the significance of miR-128-3p in tongue squamous cell carcinoma (TSCC), shedding light on its intricate functions and underlying mechanisms.
METHODS AND RESULTS
RESULTS
We quantified the expression of miR-128-3p and its target genes using qRT-PCR, followed by a series of functional assays in vitro, such as proliferation and migration assays, flow cytometry analysis, and western blotting to unravel the mechanisms underlying the functions of miR-128-3p. Additionally, we validated the ability of miR-128-3p to target MAP2K7 genes through luciferase reporter assays. We observed that increased expression of miR-128-3p significantly inhibited TSCC cell migration, proliferation, and epithelial-mesenchymal transition (EMT), possibly by regulating MAP2K7 in the JNK/MAP kinase pathway through miRNA target binding. Furthermore, we showed that increased miR-128-3p levels enhanced the sensitivity of TSCC cells to CIS through the JNK/c-Jun cascade. We observed that miR-128-3p reduces the expression of c-Jun and ABC transporter genes by targeting MAP2K7, affecting JNK1/2. This inhibition possibly decreases drug efflux and thus enhances the TSCC sensitivity to CIS treatment.
CONCLUSIONS
CONCLUSIONS
Our findings demonstrate oncosuppressive behaviour of miR-128-3p, which also potentially enhances the sensitivity of TSCC cells to CIS by suppressing MAP2K7 and JNK1/2, leading to evasion of apoptosis.
Identifiants
pubmed: 39476205
doi: 10.1007/s11033-024-10040-7
pii: 10.1007/s11033-024-10040-7
doi:
Substances chimiques
MicroRNAs
0
Cisplatin
Q20Q21Q62J
MIRN128 microRNA, human
0
MAP kinase kinase kinase 7
EC 2.7.11.25
MAP Kinase Kinase Kinases
EC 2.7.11.25
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1107Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature B.V.
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