Tags

Type your tag names separated by a space and hit enter

Increase of miR-199a-5p by protoporphyrin IX, a photocatalyzer, directly inhibits E2F3, sensitizing mesenchymal tumor cells to anti-cancer agents.
Oncotarget. 2015 Feb 28; 6(6):3918-31.O

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths. Protoporphyrin IX (PPIX) has been used for photodynamic therapy. Mesenchymal cancer cells adapt to tumor microenvironments for growth and metastasis possibly in association with miRNA dysregulation. In view of the effect of PPIX on cancer-related genes, and its potential to inhibit tumor growth and migration/invasion, this study investigated whether PPIX enables mesenchymal liver tumor to restore dysregulated miRNAs, and if so, whether it sensitizes the cancer cells to chemotherapy. In addition, we explored new target(s) of the miRNA(s) that contribute to the anti-cancer effects. Of the ten miRNAs predicted by the 3'-UTR of HIF-1α mRNA, PPIX treatment increased miR-199a-5p, leading to the inhibition of E2F3 expression which is upregulated in mesenchymal liver tumor. miR-199a-5p levels were downregulated in HCC with E2F3 overexpression. An approach modulating epithelial-mesenchymal transition provided the expected changes in miR-199a-5p and E2F3 in vivo. PPIX prevented tumor cell growth and migration/invasion, and had a synergistic anti-cancer effect when combined with chemotherapeutics. In a xenograft model, PPIX treatment decreased overall growth and average tumor volume, which paralleled E2F3 inhibition. Overall, PPIX inhibited growth advantage and migratory ability of cancer cells and sensitized mesenchymal liver tumor cells to chemotherapeutics.

Authors+Show Affiliations

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25714015

Citation

Lee, Jung Min, et al. "Increase of miR-199a-5p By Protoporphyrin IX, a Photocatalyzer, Directly Inhibits E2F3, Sensitizing Mesenchymal Tumor Cells to Anti-cancer Agents." Oncotarget, vol. 6, no. 6, 2015, pp. 3918-31.
Lee JM, Heo MJ, Lee CG, et al. Increase of miR-199a-5p by protoporphyrin IX, a photocatalyzer, directly inhibits E2F3, sensitizing mesenchymal tumor cells to anti-cancer agents. Oncotarget. 2015;6(6):3918-31.
Lee, J. M., Heo, M. J., Lee, C. G., Yang, Y. M., & Kim, S. G. (2015). Increase of miR-199a-5p by protoporphyrin IX, a photocatalyzer, directly inhibits E2F3, sensitizing mesenchymal tumor cells to anti-cancer agents. Oncotarget, 6(6), 3918-31.
Lee JM, et al. Increase of miR-199a-5p By Protoporphyrin IX, a Photocatalyzer, Directly Inhibits E2F3, Sensitizing Mesenchymal Tumor Cells to Anti-cancer Agents. Oncotarget. 2015 Feb 28;6(6):3918-31. PubMed PMID: 25714015.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increase of miR-199a-5p by protoporphyrin IX, a photocatalyzer, directly inhibits E2F3, sensitizing mesenchymal tumor cells to anti-cancer agents. AU - Lee,Jung Min, AU - Heo,Mi Jeong, AU - Lee,Chan Gyu, AU - Yang,Yoon Mee, AU - Kim,Sang Geon, PY - 2014/09/22/received PY - 2014/12/15/accepted PY - 2015/2/26/entrez PY - 2015/2/26/pubmed PY - 2016/1/14/medline SP - 3918 EP - 31 JF - Oncotarget JO - Oncotarget VL - 6 IS - 6 N2 - Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths. Protoporphyrin IX (PPIX) has been used for photodynamic therapy. Mesenchymal cancer cells adapt to tumor microenvironments for growth and metastasis possibly in association with miRNA dysregulation. In view of the effect of PPIX on cancer-related genes, and its potential to inhibit tumor growth and migration/invasion, this study investigated whether PPIX enables mesenchymal liver tumor to restore dysregulated miRNAs, and if so, whether it sensitizes the cancer cells to chemotherapy. In addition, we explored new target(s) of the miRNA(s) that contribute to the anti-cancer effects. Of the ten miRNAs predicted by the 3'-UTR of HIF-1α mRNA, PPIX treatment increased miR-199a-5p, leading to the inhibition of E2F3 expression which is upregulated in mesenchymal liver tumor. miR-199a-5p levels were downregulated in HCC with E2F3 overexpression. An approach modulating epithelial-mesenchymal transition provided the expected changes in miR-199a-5p and E2F3 in vivo. PPIX prevented tumor cell growth and migration/invasion, and had a synergistic anti-cancer effect when combined with chemotherapeutics. In a xenograft model, PPIX treatment decreased overall growth and average tumor volume, which paralleled E2F3 inhibition. Overall, PPIX inhibited growth advantage and migratory ability of cancer cells and sensitized mesenchymal liver tumor cells to chemotherapeutics. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/25714015/Increase_of_miR_199a_5p_by_protoporphyrin_IX_a_photocatalyzer_directly_inhibits_E2F3_sensitizing_mesenchymal_tumor_cells_to_anti_cancer_agents_ L2 - https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.2928 DB - PRIME DP - Unbound Medicine ER -