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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
MiR-618 inhibits anaplastic thyroid cancer by repressing XIAP in one ATC cell line
Qianpeng Cheng1, Xingguang Zhang1, Xiuping Xu1
1Department of endocrinology, The Military General Hospital of Beijing PLA, 100700 Beijing, PR China.
Abstract:
X-linked inhibitor of apoptosis protein (XIAP) is a major factor in cancer growth and progression. Reduction of XIAP induces apoptosis of anaplastic thyroid cancer (ATC), which accounts for more than 50% of thyroid cancer mortality. MicroRNAs (miRNAs) are short non-coding RNA molecules, which modulate gene expression via interaction with mRNA by binding to the 3'-untranslated region (3'-UTR), playing a critical role in cell proliferation, migration, and invasion. In this study, we recruited the ATC cell line 8305C and normal human thyroid cell Nthy-ori 3-1, aiming to find the miRNA which could regulate XIAP and therefore inhibit the growth and invasion of ATC. We first used quantitative real-time PCR (qPCR) to reveal that XIAP mRNA expression was 4.6±0.56 folds (P=0.029) up-regulated in 8305C cells, compared with Nthy-ori 3-1 cells. Then miR-618, predicted to target XIAP directly, was detected 0.24±0.06 folds (P=0.019) down-regulated in 8305C cells. Next we used Luciferase assay showing that XIAP was a target gene of miR-618, which could repress the XIAP expression at both mRNA and protein levels. After that, CCK-8 assay was performed to show that over-expression of miR-618 could inhibit the growth of 8305C cells. Finally, we employed transwell method to prove that miR-618 could prevent the invasion and migration of 8305C cells. In conclusion, our collective data showed that over-expression of miR-618 could inhibit ATC cells by targeting XIAP gene.
Insights
MicroRNA-618 (miR-618) targets X-linked inhibitor of apoptosis protein (XIAP), inhibiting anaplastic thyroid cancer (ATC) growth. Overexpressing miR-618 reduces XIAP, suppressing ATC cell proliferation and invasion.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- X-linked inhibitor of apoptosis protein (XIAP) promotes cancer progression and is upregulated in anaplastic thyroid cancer (ATC).
- MicroRNAs (miRNAs) are key regulators of gene expression involved in cell proliferation, migration, and invasion.
Purpose of the Study:
- To identify miRNAs targeting XIAP and investigate their therapeutic potential in ATC.
- To explore the role of miR-618 in regulating XIAP expression and its impact on ATC cell behavior.
Main Methods:
- Quantitative real-time PCR (qPCR) to assess XIAP and miR-618 expression levels.
- Luciferase assay to confirm XIAP as a direct target of miR-618.
- CCK-8 and Transwell assays to evaluate the effects of miR-618 overexpression on ATC cell growth, invasion, and migration.
Main Results:
- XIAP mRNA was significantly upregulated in ATC cells (8305C) compared to normal thyroid cells (Nthy-ori 3-1).
- miR-618 was significantly downregulated in ATC cells and directly targeted XIAP, repressing its expression at mRNA and protein levels.
- Overexpression of miR-618 inhibited 8305C cell proliferation, invasion, and migration.
Conclusions:
- miR-618 acts as a tumor suppressor in ATC by targeting XIAP.
- miR-618 holds potential as a therapeutic agent for inhibiting anaplastic thyroid cancer growth and metastasis.

