Home Journals MicroRNA-342-3p is a potent tumour suppressor in hepatocellular carcinoma

MicroRNA-342-3p is a potent tumour suppressor in hepatocellular carcinoma

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MicroRNA-342-3p is a potent tumour suppressor in hepatocellular carcinoma

Background & Aims

Hepatocellular carcinoma (HCC) is a cancer with multiple etiologies, and widespread
prevalence. Largely refractory to current treatments, HCC is the fourth leading cause
of cancer related deaths, world-wide. MicroRNAs (miRNAs) are important regulators
in HCCs. We aimed to identify tumor suppressor miRNAs during tumor regression in a
conditional c-MYC driven mouse model (LT2/MYC) of HCC, and to evaluate their therapeutic
potential for HCC treatment

Methods

We performed miRNA expression profiling of developed and regressing LT2/MYC tumors,
and in-depth
in vitro gain- and loss-of-function analyses. Effect of adeno-associated virus vector (AAV)-mediated
miR-342-3p treatment was evaluated in three HCC mouse models

Results

We identified miR-342-3p as a tumor suppressor miRNA in HCC, with increased expression
in regressing tumors. Forced miR-342-3p expression in hepatoma cells showed significantly
decreased cell proliferation, migration and colony formation.
In vivo administration of AAV-miR-342-3p led to significant attenuation of tumor development
and increased overall survival. We identified
Mct1 as a
bona fide target of miR-342-3p in HCC. We show the tumor suppressor role of miR-342-3p is executed
partly by modulating the lactate transport function of MCT1. Importantly, we find
miR-342-3p downregulated in tumors from HCC patients compared to matched non-tumor
tissues, inversely correlating with MCT1 expression. We observed similar findings
in TCGA-LIHC data.

Conclusion

In our study, we identified and validated miR-342-3p as a tumor suppressor miRNA,
in HCC. We demonstrated its therapeutic efficacy in significantly attenuating tumor
development, and prolonging survival, in different HCC mouse models. Identification
of miR-342-3p as an effective tumor suppressor opens a therapeutic avenue for miRNA-mediated
attenuation of HCC development.

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