MicroRNA-140-5p inhibits cellular proliferation, migration and invasion by downregulating AKT/STAT3/NF-κB pathway in breast carcinoma cells

MicroRNA-140-5p (miR-140-5p) plays a pivotal role in human cancers. However, its role and molecular mechanisms in breast carcinoma are not fully explored. Using miR-140-5p transfected breast cancer cell line MDA-MB-231, several in vitro experiments were performed and described in this paper. They co...

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Main Authors: Hou Lingli, Liu Qi, Zhao Ying, Yang Hongwei, Meng Qingying, Yu Fei
Format: Article
Language:English
Published: Sciendo 2022-12-01
Series:Acta Pharmaceutica
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Online Access:https://doi.org/10.2478/acph-2022-0039
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author Hou Lingli
Liu Qi
Zhao Ying
Yang Hongwei
Meng Qingying
Yu Fei
author_facet Hou Lingli
Liu Qi
Zhao Ying
Yang Hongwei
Meng Qingying
Yu Fei
author_sort Hou Lingli
collection DOAJ
description MicroRNA-140-5p (miR-140-5p) plays a pivotal role in human cancers. However, its role and molecular mechanisms in breast carcinoma are not fully explored. Using miR-140-5p transfected breast cancer cell line MDA-MB-231, several in vitro experiments were performed and described in this paper. They consist of the cell proliferation assay, wound healing assay, transwell assay, colony formation assays and qRTPCR. Expression levels of target proteins were determined using Western blotting. In addition, experiments on animal models were performed to study the possible role of miR-140-5p in tumorigenesis of breast carcinoma cells. The induction of experimental breast tumor in mice model was achieved through the incorporation of MDA-MB-231 tumor cells subcutaneously into the middle left side of the mice. The results showed that miR-140-5p up-regulation significantly suppresses proliferation, cellular invasion and migration of breast carcinoma cells. Furthermore, miR-140-5p up-regulation stops breast cancer cells at G0/G1 phase. The results of the animal model indicated that up-regulation of miR-140-5p suppresses its tumorigenic ability. Moreover, we also found that miR-140-5p up-regulation reduces the phosphorylation level of STAT3, p65, and AKT. In addition, miR-140-5p overexpression significantly decreases CDK2 expression while increasing E-cadherin expression level. These data revealed that miR-140-5p suppressed tumor progression of breast carcinoma cells through inhibition of the AKT/STAT3/NF-κB pathway. Taken the present study results together, we can conclude that miR-140-5p may act as a novel target in microRNA-targeting anticancer strategy for the treatment of breast cancer.
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spelling doaj-art-2d81e11ddb4a4102b7c20ccf08091a102025-02-03T06:37:53ZengSciendoActa Pharmaceutica1846-95582022-12-0172458759710.2478/acph-2022-0039MicroRNA-140-5p inhibits cellular proliferation, migration and invasion by downregulating AKT/STAT3/NF-κB pathway in breast carcinoma cellsHou Lingli0Liu Qi1Zhao Ying2Yang Hongwei3Meng Qingying4Yu Fei5Department of Clinical Laboratory, Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, Shiyan City Hubei Province, 442000, P.R.ChinaDepartment of Human Anatomy, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan City Hubei Province, 442000, P.R.ChinaDepartment of Clinical Laboratory, Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, Shiyan City Hubei Province, 442000, P.R.ChinaDepartment of Clinical Laboratory, Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, Shiyan City Hubei Province, 442000, P.R.ChinaDepartment of Medical Insurance, Yunxi People’s Hospital, Yunxi, Hubei Province 442600, P.R.ChinaDepartment of Clinical Laboratory, Yunxi People’s Hospital, Yunxi, Hubei Province442600, P.R.ChinaMicroRNA-140-5p (miR-140-5p) plays a pivotal role in human cancers. However, its role and molecular mechanisms in breast carcinoma are not fully explored. Using miR-140-5p transfected breast cancer cell line MDA-MB-231, several in vitro experiments were performed and described in this paper. They consist of the cell proliferation assay, wound healing assay, transwell assay, colony formation assays and qRTPCR. Expression levels of target proteins were determined using Western blotting. In addition, experiments on animal models were performed to study the possible role of miR-140-5p in tumorigenesis of breast carcinoma cells. The induction of experimental breast tumor in mice model was achieved through the incorporation of MDA-MB-231 tumor cells subcutaneously into the middle left side of the mice. The results showed that miR-140-5p up-regulation significantly suppresses proliferation, cellular invasion and migration of breast carcinoma cells. Furthermore, miR-140-5p up-regulation stops breast cancer cells at G0/G1 phase. The results of the animal model indicated that up-regulation of miR-140-5p suppresses its tumorigenic ability. Moreover, we also found that miR-140-5p up-regulation reduces the phosphorylation level of STAT3, p65, and AKT. In addition, miR-140-5p overexpression significantly decreases CDK2 expression while increasing E-cadherin expression level. These data revealed that miR-140-5p suppressed tumor progression of breast carcinoma cells through inhibition of the AKT/STAT3/NF-κB pathway. Taken the present study results together, we can conclude that miR-140-5p may act as a novel target in microRNA-targeting anticancer strategy for the treatment of breast cancer.https://doi.org/10.2478/acph-2022-0039breast cancermicrorna-140-5pcell proliferationtumor progressionakt/stat3/nf-κb
spellingShingle Hou Lingli
Liu Qi
Zhao Ying
Yang Hongwei
Meng Qingying
Yu Fei
MicroRNA-140-5p inhibits cellular proliferation, migration and invasion by downregulating AKT/STAT3/NF-κB pathway in breast carcinoma cells
Acta Pharmaceutica
breast cancer
microrna-140-5p
cell proliferation
tumor progression
akt/stat3/nf-κb
title MicroRNA-140-5p inhibits cellular proliferation, migration and invasion by downregulating AKT/STAT3/NF-κB pathway in breast carcinoma cells
title_full MicroRNA-140-5p inhibits cellular proliferation, migration and invasion by downregulating AKT/STAT3/NF-κB pathway in breast carcinoma cells
title_fullStr MicroRNA-140-5p inhibits cellular proliferation, migration and invasion by downregulating AKT/STAT3/NF-κB pathway in breast carcinoma cells
title_full_unstemmed MicroRNA-140-5p inhibits cellular proliferation, migration and invasion by downregulating AKT/STAT3/NF-κB pathway in breast carcinoma cells
title_short MicroRNA-140-5p inhibits cellular proliferation, migration and invasion by downregulating AKT/STAT3/NF-κB pathway in breast carcinoma cells
title_sort microrna 140 5p inhibits cellular proliferation migration and invasion by downregulating akt stat3 nf κb pathway in breast carcinoma cells
topic breast cancer
microrna-140-5p
cell proliferation
tumor progression
akt/stat3/nf-κb
url https://doi.org/10.2478/acph-2022-0039
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