American Association for Cancer Research
15417786mcr140703-sup-142925_1_supp_2876425_nkc00k.xlsx (45.5 kB)

Supplementary Data 1 from Anti–miR-21 Suppresses Hepatocellular Carcinoma Growth via Broad Transcriptional Network Deregulation

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posted on 2023-04-03, 17:00 authored by Timothy R. Wagenaar, Sonya Zabludoff, Sung-Min Ahn, Charles Allerson, Heike Arlt, Raffaele Baffa, Hui Cao, Scott Davis, Carlos Garcia-Echeverria, Rajula Gaur, Shih-Min A. Huang, Lan Jiang, Deokhoon Kim, Christiane Metz-Weidmann, Adam Pavlicek, Jack Pollard, Jason Reeves, Jennifer L. Rocnik, Sabine Scheidler, Chaomei Shi, Fangxian Sun, Tatiana Tolstykh, William Weber, Christopher Winter, Eunsil Yu, Qunyan Yu, Gang Zheng, Dmitri Wiederschain

Supplementary Data 1. Excel sheet with fold change in gene expression following anti-miR-21 treatment.



Hepatocellular carcinoma (HCC) remains a significant clinical challenge with few therapeutic options available to cancer patients. MicroRNA 21-5p (miR-21) has been shown to be upregulated in HCC, but the contribution of this oncomiR to the maintenance of tumorigenic phenotype in liver cancer remains poorly understood. We have developed potent and specific single-stranded oligonucleotide inhibitors of miR-21 (anti-miRNAs) and used them to interrogate dependency on miR-21 in a panel of liver cancer cell lines. Treatment with anti–miR-21, but not with a mismatch control anti-miRNA, resulted in significant derepression of direct targets of miR-21 and led to loss of viability in the majority of HCC cell lines tested. Robust induction of caspase activity, apoptosis, and necrosis was noted in anti–miR-21-treated HCC cells. Furthermore, ablation of miR-21 activity resulted in inhibition of HCC cell migration and suppression of clonogenic growth. To better understand the consequences of miR-21 suppression, global gene expression profiling was performed on anti–miR-21-treated liver cancer cells, which revealed striking enrichment in miR-21 target genes and deregulation of multiple growth-promoting pathways. Finally, in vivo dependency on miR-21 was observed in two separate HCC tumor xenograft models. In summary, these data establish a clear role for miR-21 in the maintenance of tumorigenic phenotype in HCC in vitro and in vivo.Implications: miR-21 is important for the maintenance of the tumorigenic phenotype of HCC and represents a target for pharmacologic intervention. Mol Cancer Res; 13(6); 1009–21. ©2015 AACR.

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