Lactate induces aberration in the miR-30a–DBF4 axis to promote the development of gastric cancer and weakens the sensitivity to 5-Fu

Abstract Background Gastric cancer (GC) is one of the most common malignancies, molecular mechanism of which is still not clear. Aberrant expression of tumor-associated genes is the major cause of tumorigenesis. DBF4 is an important factor in cancers, although there is yet no report on its function...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Tengkai Wang, Rui Ji, Guanqun Liu, Beilei Ma, Zehua Wang, Qian Wang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Gastric cancer DBF4 miR-30a Lactate Proliferation migration,5-Fu Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/4e62a756e9114bdb9f748b55f8914f7f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4e62a756e9114bdb9f748b55f8914f7f
record_format	dspace
spelling	oai:doaj.org-article:4e62a756e9114bdb9f748b55f8914f7f2021-11-14T12:37:35ZLactate induces aberration in the miR-30a–DBF4 axis to promote the development of gastric cancer and weakens the sensitivity to 5-Fu10.1186/s12935-021-02291-21475-2867https://doaj.org/article/4e62a756e9114bdb9f748b55f8914f7f2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12935-021-02291-2https://doaj.org/toc/1475-2867Abstract Background Gastric cancer (GC) is one of the most common malignancies, molecular mechanism of which is still not clear. Aberrant expression of tumor-associated genes is the major cause of tumorigenesis. DBF4 is an important factor in cancers, although there is yet no report on its function and molecular mechanism in GC. Methods The expression of DBF4 in tumor tissues or cells of GC was detected by qRT-PCR and western blotting. Gastric cancer cell line MGC-803 and AGS were transfected with DBF4 siRNA or overexpression vector to detect the function of DBF4 in proliferation, migration and the sensitivity to 5-Fu with CCK-8 assay, colony formation assay, transwell assay, and wound healing assay. miR-30a was found to be the regulator of DBF4 by online bioinformatics software and confirmed with qRT-PCR, western blot and dual-luciferase reporter assays. Results In our study, increased expression of DBF4 in GC tissues was first identified through The Cancer Genome Atlas (TCGA) and later confirmed using specimens from GC patients. Furthermore, functional experiments were applied to demonstrate that DBF4 promotes cell proliferation and migration in GC cell lines, moreover weakens the sensitivity of MGC803 and AGS cells to 5-Fu. We further demonstrated that miR-30a showed significantly lower expression in GC cells and inhibited the expression of DBF4 through 3ʹ-UTR suppression. Furthermore, rescue experiments revealed that the miR-30a-DBF4 axis regulated the GC cell proliferation, migration and the sensitivity to 5-Fu. The important composition in tumor microenvironment, lactate, may be the primary factor that suppressed miR-30a to strengthen the expression of DBF4. Conclusions Taken together, our study was the first to identify DBF4 as a regulator of cell proliferation and migration in GC. Furthermore, our study identified the lactate-miR-30a-DBF4 axis as a crucial regulator of tumor progression and the tumor sensitivity to 5-Fu, which maybe serve useful for the development of novel therapeutic targets.Tengkai WangRui JiGuanqun LiuBeilei MaZehua WangQian WangBMCarticleGastric cancerDBF4miR-30aLactateProliferationmigration,5-FuNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCancer Cell International, Vol 21, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Gastric cancer DBF4 miR-30a Lactate Proliferation migration,5-Fu Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	Gastric cancer DBF4 miR-30a Lactate Proliferation migration,5-Fu Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Tengkai Wang Rui Ji Guanqun Liu Beilei Ma Zehua Wang Qian Wang Lactate induces aberration in the miR-30a–DBF4 axis to promote the development of gastric cancer and weakens the sensitivity to 5-Fu
description	Abstract Background Gastric cancer (GC) is one of the most common malignancies, molecular mechanism of which is still not clear. Aberrant expression of tumor-associated genes is the major cause of tumorigenesis. DBF4 is an important factor in cancers, although there is yet no report on its function and molecular mechanism in GC. Methods The expression of DBF4 in tumor tissues or cells of GC was detected by qRT-PCR and western blotting. Gastric cancer cell line MGC-803 and AGS were transfected with DBF4 siRNA or overexpression vector to detect the function of DBF4 in proliferation, migration and the sensitivity to 5-Fu with CCK-8 assay, colony formation assay, transwell assay, and wound healing assay. miR-30a was found to be the regulator of DBF4 by online bioinformatics software and confirmed with qRT-PCR, western blot and dual-luciferase reporter assays. Results In our study, increased expression of DBF4 in GC tissues was first identified through The Cancer Genome Atlas (TCGA) and later confirmed using specimens from GC patients. Furthermore, functional experiments were applied to demonstrate that DBF4 promotes cell proliferation and migration in GC cell lines, moreover weakens the sensitivity of MGC803 and AGS cells to 5-Fu. We further demonstrated that miR-30a showed significantly lower expression in GC cells and inhibited the expression of DBF4 through 3ʹ-UTR suppression. Furthermore, rescue experiments revealed that the miR-30a-DBF4 axis regulated the GC cell proliferation, migration and the sensitivity to 5-Fu. The important composition in tumor microenvironment, lactate, may be the primary factor that suppressed miR-30a to strengthen the expression of DBF4. Conclusions Taken together, our study was the first to identify DBF4 as a regulator of cell proliferation and migration in GC. Furthermore, our study identified the lactate-miR-30a-DBF4 axis as a crucial regulator of tumor progression and the tumor sensitivity to 5-Fu, which maybe serve useful for the development of novel therapeutic targets.
format	article
author	Tengkai Wang Rui Ji Guanqun Liu Beilei Ma Zehua Wang Qian Wang
author_facet	Tengkai Wang Rui Ji Guanqun Liu Beilei Ma Zehua Wang Qian Wang
author_sort	Tengkai Wang
title	Lactate induces aberration in the miR-30a–DBF4 axis to promote the development of gastric cancer and weakens the sensitivity to 5-Fu
title_short	Lactate induces aberration in the miR-30a–DBF4 axis to promote the development of gastric cancer and weakens the sensitivity to 5-Fu
title_full	Lactate induces aberration in the miR-30a–DBF4 axis to promote the development of gastric cancer and weakens the sensitivity to 5-Fu
title_fullStr	Lactate induces aberration in the miR-30a–DBF4 axis to promote the development of gastric cancer and weakens the sensitivity to 5-Fu
title_full_unstemmed	Lactate induces aberration in the miR-30a–DBF4 axis to promote the development of gastric cancer and weakens the sensitivity to 5-Fu
title_sort	lactate induces aberration in the mir-30a–dbf4 axis to promote the development of gastric cancer and weakens the sensitivity to 5-fu
publisher	BMC
publishDate	2021
url	https://doaj.org/article/4e62a756e9114bdb9f748b55f8914f7f
work_keys_str_mv	AT tengkaiwang lactateinducesaberrationinthemir30adbf4axistopromotethedevelopmentofgastriccancerandweakensthesensitivityto5fu AT ruiji lactateinducesaberrationinthemir30adbf4axistopromotethedevelopmentofgastriccancerandweakensthesensitivityto5fu AT guanqunliu lactateinducesaberrationinthemir30adbf4axistopromotethedevelopmentofgastriccancerandweakensthesensitivityto5fu AT beileima lactateinducesaberrationinthemir30adbf4axistopromotethedevelopmentofgastriccancerandweakensthesensitivityto5fu AT zehuawang lactateinducesaberrationinthemir30adbf4axistopromotethedevelopmentofgastriccancerandweakensthesensitivityto5fu AT qianwang lactateinducesaberrationinthemir30adbf4axistopromotethedevelopmentofgastriccancerandweakensthesensitivityto5fu
_version_	1718429104462626816

Lactate induces aberration in the miR-30a–DBF4 axis to promote the development of gastric cancer and weakens the sensitivity to 5-Fu

Ejemplares similares