MicroRNA-138 enhances TRAIL-induced apoptosis through interferon-stimulated gene 15 downregulation in hepatocellular carcinoma cells

Chaohui Zuo, Xinyi Sheng, Zhuo Liu, Min Ma, Shuhan Xiong, Hongyu Deng, Sha Li, Darong Yang, Xiaohong Wang, Hua Xiao, Hu Quan, Man Xia

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Abstract

Hepatocellular carcinoma is a leading cause of cancer-related mortality worldwide. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a potential target for cancer therapy. However, many cancer cells are resistant to TRAIL-induced apoptosis and its mechanism is not well understood. In this study, to identify potential therapeutic targets for TRAIL-resistant cancer cells, we compared the expression levels of interferon-stimulated gene 15 in TRAIL-sensitive and TRAIL-resistant hepatocellular carcinoma cell lines. Western blot analysis showed that interferon-stimulated gene 15 expression levels were significantly higher in resistant HLCZ01and Huh7 cells than in sensitive LH86 and SMMC-7721 cells. Interferon-stimulated gene 15 knockdown in resistance cells led to TRAIL sensitivity. Conversely, interferonstimulated gene 15 overexpression in sensitive cells resulted in TRAIL resistance. Our bioinformatics search detected a putative target sequence for microRNA miR-138 in the 3′ untranslated region of the interferon-stimulated gene 15. Real-time quantitative polymerase chain reaction analysis demonstrated that miR-138 was significantly downregulated in TRAIL-resistant cells compared to TRAIL-sensitive cells. Forced expression of miR-138 in resistant cells decreased both messenger RNA and protein levels of interferon-stimulated gene 15, and when exposed to TRAIL, activated poly(adenosine diphosphate-ribose) polymerase, indicating sensitization to TRAIL. The results suggested that miR-138 regulates the interferon-stimulated gene 15 expression by directly targeting the 3′ untranslated region of interferonstimulated gene 15 and modulates the sensitivity to TRAIL-induced apoptosis. MiR-138 may be a target for therapeutic intervention in TRAIL-based drug treatments of resistant hepatocellular carcinoma or could be a biomarker to select patients who may benefit from the treatment.

Original languageEnglish (US)
JournalTumor Biology
Volume39
Issue number6
DOIs
StatePublished - Jan 1 2017

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MicroRNAs
Interferons
Hepatocellular Carcinoma
Down-Regulation
Apoptosis
Genes
3' Untranslated Regions
Neoplasms
Poly Adenosine Diphosphate Ribose
Gene Knockdown Techniques
Therapeutics
Gene Expression
Computational Biology
Real-Time Polymerase Chain Reaction
Tumor Necrosis Factor-alpha
Biomarkers
Western Blotting
Ligands
Cell Line
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Cancer Research

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MicroRNA-138 enhances TRAIL-induced apoptosis through interferon-stimulated gene 15 downregulation in hepatocellular carcinoma cells. / Zuo, Chaohui; Sheng, Xinyi; Liu, Zhuo; Ma, Min; Xiong, Shuhan; Deng, Hongyu; Li, Sha; Yang, Darong; Wang, Xiaohong; Xiao, Hua; Quan, Hu; Xia, Man.

In: Tumor Biology, Vol. 39, No. 6, 01.01.2017.

Research output: Contribution to journalArticle

Zuo, Chaohui ; Sheng, Xinyi ; Liu, Zhuo ; Ma, Min ; Xiong, Shuhan ; Deng, Hongyu ; Li, Sha ; Yang, Darong ; Wang, Xiaohong ; Xiao, Hua ; Quan, Hu ; Xia, Man. / MicroRNA-138 enhances TRAIL-induced apoptosis through interferon-stimulated gene 15 downregulation in hepatocellular carcinoma cells. In: Tumor Biology. 2017 ; Vol. 39, No. 6.
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AU - Ma, Min

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AU - Deng, Hongyu

AU - Li, Sha

AU - Yang, Darong

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