Hypoxia-Induced Downregulation of miR-29 in Renal Tumor Cells Affects Collagen IV Subunit Expression through Multiple Sites

Multiple tumor exacerbations and treatment procedures, such as extracellular matrix remodeling, metabolic reprogramming, immunological evasion, and resistance to chemotherapy and radiotherapy, are influenced by intratumoral hypoxia. It is becoming increasingly clear how hypoxia interacts with the ex...

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Main Authors: Chuncheng Liu, Linan Liu, Jinlai Bo, Xian Lu, Donghui Qu, Gehui Liu, Zhiyan Jiang, Lu Cai
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/10/12/3286
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author Chuncheng Liu
Linan Liu
Jinlai Bo
Xian Lu
Donghui Qu
Gehui Liu
Zhiyan Jiang
Lu Cai
author_facet Chuncheng Liu
Linan Liu
Jinlai Bo
Xian Lu
Donghui Qu
Gehui Liu
Zhiyan Jiang
Lu Cai
author_sort Chuncheng Liu
collection DOAJ
description Multiple tumor exacerbations and treatment procedures, such as extracellular matrix remodeling, metabolic reprogramming, immunological evasion, and resistance to chemotherapy and radiotherapy, are influenced by intratumoral hypoxia. It is becoming increasingly clear how hypoxia interacts with the extracellular matrix and how this affects the growth of cancer. We analyzed the published sequencing results of hypoxia-stressed mouse kidney tumor cells and found that the expression of miR-29b was significantly downregulated. There are several sites that are complementary to the miR-29 seed sequence in the 3’ non-coding regions (3’UTRs) of various extracellular matrix-related genes, including collagen IV. We analyzed the sequences of the 3’UTRs of different subunits of collagen IV in different species and constructed the corresponding phylogenetic trees. We found that the 3’UTRs of <i>Col4a1</i> and <i>Col4a4</i> may have been subjected to particular evolutionary pressures. By cloning the 3’UTRs of collagen IV subunits into the psiCHECK<sup>TM</sup>-2 vector, we found that seven of the eight sites in the <i>Col4a3</i>–<i>Col4a6</i> gene complementary to miR-29 were significantly repressed by miR-29a, b (except for the 7774–7781 of <i>Col4a3</i> gene). The inhibitory efficiency of miR-29a, b on these seven sites was between 27% and 57%. The research on the regulation of miR-29 and extracellular matrix by hypoxia can provide a theoretical basis for tumor and fibrosis research and treatment.
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spelling doaj.art-29b19c95f1ca40f0b719e610efca1a252023-11-24T13:30:04ZengMDPI AGBiomedicines2227-90592022-12-011012328610.3390/biomedicines10123286Hypoxia-Induced Downregulation of miR-29 in Renal Tumor Cells Affects Collagen IV Subunit Expression through Multiple SitesChuncheng Liu0Linan Liu1Jinlai Bo2Xian Lu3Donghui Qu4Gehui Liu5Zhiyan Jiang6Lu Cai7School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou 014010, ChinaSchool of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou 014010, ChinaSchool of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou 014010, ChinaSchool of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou 014010, ChinaSchool of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou 014010, ChinaSchool of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou 014010, ChinaSchool of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou 014010, ChinaSchool of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou 014010, ChinaMultiple tumor exacerbations and treatment procedures, such as extracellular matrix remodeling, metabolic reprogramming, immunological evasion, and resistance to chemotherapy and radiotherapy, are influenced by intratumoral hypoxia. It is becoming increasingly clear how hypoxia interacts with the extracellular matrix and how this affects the growth of cancer. We analyzed the published sequencing results of hypoxia-stressed mouse kidney tumor cells and found that the expression of miR-29b was significantly downregulated. There are several sites that are complementary to the miR-29 seed sequence in the 3’ non-coding regions (3’UTRs) of various extracellular matrix-related genes, including collagen IV. We analyzed the sequences of the 3’UTRs of different subunits of collagen IV in different species and constructed the corresponding phylogenetic trees. We found that the 3’UTRs of <i>Col4a1</i> and <i>Col4a4</i> may have been subjected to particular evolutionary pressures. By cloning the 3’UTRs of collagen IV subunits into the psiCHECK<sup>TM</sup>-2 vector, we found that seven of the eight sites in the <i>Col4a3</i>–<i>Col4a6</i> gene complementary to miR-29 were significantly repressed by miR-29a, b (except for the 7774–7781 of <i>Col4a3</i> gene). The inhibitory efficiency of miR-29a, b on these seven sites was between 27% and 57%. The research on the regulation of miR-29 and extracellular matrix by hypoxia can provide a theoretical basis for tumor and fibrosis research and treatment.https://www.mdpi.com/2227-9059/10/12/3286miR-29collagen IVextracellular matrix3’UTRhypoxia
spellingShingle Chuncheng Liu
Linan Liu
Jinlai Bo
Xian Lu
Donghui Qu
Gehui Liu
Zhiyan Jiang
Lu Cai
Hypoxia-Induced Downregulation of miR-29 in Renal Tumor Cells Affects Collagen IV Subunit Expression through Multiple Sites
Biomedicines
miR-29
collagen IV
extracellular matrix
3’UTR
hypoxia
title Hypoxia-Induced Downregulation of miR-29 in Renal Tumor Cells Affects Collagen IV Subunit Expression through Multiple Sites
title_full Hypoxia-Induced Downregulation of miR-29 in Renal Tumor Cells Affects Collagen IV Subunit Expression through Multiple Sites
title_fullStr Hypoxia-Induced Downregulation of miR-29 in Renal Tumor Cells Affects Collagen IV Subunit Expression through Multiple Sites
title_full_unstemmed Hypoxia-Induced Downregulation of miR-29 in Renal Tumor Cells Affects Collagen IV Subunit Expression through Multiple Sites
title_short Hypoxia-Induced Downregulation of miR-29 in Renal Tumor Cells Affects Collagen IV Subunit Expression through Multiple Sites
title_sort hypoxia induced downregulation of mir 29 in renal tumor cells affects collagen iv subunit expression through multiple sites
topic miR-29
collagen IV
extracellular matrix
3’UTR
hypoxia
url https://www.mdpi.com/2227-9059/10/12/3286
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