Ferritin Light Chain (FTL) competes with long noncoding RNA Linc00467 for miR-133b binding site to regulate chemoresistance and metastasis of colorectal cancer.

Abstract

Although the colorectal cancer (CRC) mortality rates are decreasing in virtue of CRC screening and improved therapeutic methods, CRC is still a leading cause of cancer deaths. One of the main causes is chemoresistance occurrence in CRC. Understanding of the molecular mechanisms of chemoresistance benefits to CRC diagnosis and treatment. In this study, gene expression was determined by western blot and qRT-PCR. The biological functions of genes in CRC cells were studied by knocking down or overexpressing the gene in CRC cells and then analyzing cell sensitivity to 5-Fu by the MTT assay and the flow cytometry, and analyzing cell migration and invasion by transwell assays. The luciferase reporter assay was used to examine microRNA regulation of target gene expression, and biotin pull-down assay was performed to detect interaction between RNA molecules. This study found that ferritin light chain (FTL) and long intergenic noncoding RNA Linc00467 were both upregulated in CRC tissues and cell lines, and inversely correlated to CRC patient survival. FTL and Linc00467 promoted CRC cells abilities to resistance against 5-fluor-ouracil (5-Fu), migration and invasion. These effects were compromised by miR-133b which targeted both FTL and Linc00467. miR-133b interacted with Linc00467 and miR-133b inhibitor prevented Linc00467 knockdown-induced alternations of FTL expression and biological functions. Both FTL and Linc00467 are oncogenes in CRC. FTL expression upregulated in CRC via Linc00467/ miR-133b axis, and leads to CRC cell resistance against 5-FU treatment and promotes CRC metastasis. FTL expression upregulated in CRC via Linc00467/miR-133b axis, and leads to CRC cell resistance to 5-FU treatment and promotes CRC metastasis.

• Authors: Zengyao Li, Jing Liu, Hang Chen, Ye Zhang, Haoze Shi, Longchang Huang, Jianxin Tao, Renhui Shen, Tong Wang
• Journal: Carcinogenesis (Carcinogenesis) Vol. 41 Issue 4 Pg. 467-477 (06 17 2020) ISSN: 1460-2180 [Electronic] England
• PMID: 31675755 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Antimetabolites, Antineoplastic
• Biomarkers, Tumor
• FTL protein, human
• MIRN133 microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• Apoferritins
• Fluorouracil

Topics

• Animals
• Antimetabolites, Antineoplastic (pharmacology)
• Apoferritins (genetics, metabolism)
• Apoptosis
• Binding Sites
• Biomarkers, Tumor (genetics, metabolism)
• Cell Proliferation
• Colorectal Neoplasms (drug therapy, genetics, metabolism, pathology)
• Drug Resistance, Neoplasm (genetics)
• Fluorouracil (pharmacology)
• Gene Expression Regulation, Neoplastic
• Humans
• Liver Neoplasms (drug therapy, genetics, metabolism, secondary)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics)
• Prognosis
• RNA, Long Noncoding (genetics)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays