Long noncoding RNA LINC00483/microRNA‐144 regulates radiosensitivity and epithelial–mesenchymal transition in lung adenocarcinoma by interacting with HOXA10

Autor: Si‐Qi Yang, Qing‐Shan Yang, Bin Li, Peng Wang, Huai‐Hui Tang, Yuan‐Yuan Liu, Ge Xu
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Epithelial-Mesenchymal Transition
Lung Neoplasms
Carcinogenesis
Physiology
Clinical Biochemistry
Cell
Down-Regulation
Mice
Nude
Adenocarcinoma of Lung
Vimentin
Binding
Competitive
Models
Biological
Radiation Tolerance
03 medical and health sciences
0302 clinical medicine
Cell Movement
Cell Line
Tumor
microRNA
medicine
Animals
Humans
Gene silencing
Neoplasm Invasiveness
Gene Silencing
Epithelial–mesenchymal transition
Cell Proliferation
Base Sequence
biology
Cell growth
Microarray analysis techniques
Cell Biology
Middle Aged
Long non-coding RNA
Up-Regulation
Gene Expression Regulation
Neoplastic
MicroRNAs
Homeobox A10 Proteins
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Cancer research
biology.protein
Female
RNA
Long Noncoding
Zdroj: Journal of Cellular Physiology. 234:11805-11821
ISSN: 1097-4652
0021-9541
DOI: 10.1002/jcp.27886
Popis: Lung adenocarcinoma (LAD) is the leading cause of cancer death worldwide. Long noncoding RNAs (lncRNAs) have been shown to play an important regulatory role in cancer biology, including that of LAD. The aim of this experiment was to explore the interaction of LINC00483, microRNA-144 (miR-144), and homeobox A10 (HOXA10), and their effects on radio sensitivity and epithelial-mesenchymal transition (EMT) of LAD. Initially, microarray analysis was used to screen out miRNAs and lncRNAs, as well as the differentially expressed genes related to LAD. Following the screening process, the targeting relationship of LINC00483, miR-144, and that of miR-144 and HOXA10 was determined. Following that, the expression of LINC00483, miR-144, messenger RNA (mRNA), as well as protein expression of HOXA10, MMP-2, MMP-9, E-cadherin, vimentin, and N-cadherin that followed in cells was determined. Also, the effect of LINC00483 on cell migration and invasion ability, and cell tumorigenic ability was detected. LINC00483 and HOXA10 were found to be upregulated whereas miR-144 was downregulated in LAD. Silencing of LINC00483 could competitively bind to miR-144, thereby upregulating HOXA10. LINC00483 or HOXA10 silencing led to decreased HOXA10, MMP-2, MMP-9, vimentin, and N-cadherin but elevated miR-144 and E-cadherin. Moreover, after being transfected with silenced LINC00483, the cell proliferation, migration, and invasion were inhibited with enhanced radiosensitivity. Consequently, the data of the study indicates that interference of LINC00483 weakens its competitive binding ability to miR-144, thus reducing HOXA10 expression, and enhancing radiosensitivity in LAD.
Databáze: OpenAIRE
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