Splicing factor hnRNPA2B1 contributes to tumorigenic potential of breast cancer cells through STAT3 and ERK1/2 signaling pathway

Increasing evidence has indicated that the splicing factor hnRNPA2B1 plays a direct role in cancer development, progression, gene expression, and signal transduction. Previous studies have shown that knocking down hnRNPA2B1 in breast cancer cells induces apoptosis, but the mechanism and other functi...

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Main Authors: Ying Hu, Zihan Sun, Jinmu Deng, Baoquan Hu, Wenting Yan, Hongyi Wei, Jun Jiang
Format: Article
Language:English
Published: SAGE Publishing 2017-03-01
Series:Tumor Biology
Online Access:https://doi.org/10.1177/1010428317694318
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author Ying Hu
Zihan Sun
Jinmu Deng
Baoquan Hu
Wenting Yan
Hongyi Wei
Jun Jiang
author_facet Ying Hu
Zihan Sun
Jinmu Deng
Baoquan Hu
Wenting Yan
Hongyi Wei
Jun Jiang
author_sort Ying Hu
collection DOAJ
description Increasing evidence has indicated that the splicing factor hnRNPA2B1 plays a direct role in cancer development, progression, gene expression, and signal transduction. Previous studies have shown that knocking down hnRNPA2B1 in breast cancer cells induces apoptosis, but the mechanism and other functions of hnRNPA2B1 in breast cancer are unknown. The goal of this study was to investigate the biological function, clinical significance, and mechanism of hnRNPA2B1 in breast cancer. The expression of hnRNPA2B1 in 92 breast cancer and adjacent normal tissue pairs was analyzed by immunohistochemical staining. Stable clones exhibiting knockdown of hnRNPA2B1 via small hairpin RNA expression were generated using RNA interference technology in breast cancer cell lines. The effects of hnRNPA2B1 on cell proliferation were examined by MTT and EdU assay, and cellular apoptosis and the cell cycle were examined by flow cytometry. A nude mouse xenograft model was established to elucidate the function of hnRNPA2B1 in tumorigenesis in vivo. The role of hnRNPA2B1 in signaling pathways was investigated in vitro. Our data revealed that hnRNPA2B1 was overexpressed in breast cancer tissue specimens and cell lines. Knockdown of hnRNPA2B1 reduced breast cancer cell proliferation, induced apoptosis, and prolonged the S phase of the cell cycle in vitro. In addition, hnRNPA2B1 knockdown suppressed subcutaneous tumorigenicity in vivo. On a molecular level, hnRNPA2B1 knockdown decreased signal transducer and activator of transcription 3 and extracellular-signal-regulated kinase 1/2 phosphorylation. We concluded that hnRNPA2B1 promotes the tumorigenic potential of breast cancer cells, MCF-7 and MDA-MB-231, through the extracellular-signal-regulated kinase 1/2 or signal transducer and activator of transcription 3 pathway, which may serve as a target for future therapies.
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spelling doaj-art-4eccd80fb30f4fbcae065cb283bd859d2025-08-20T03:58:22ZengSAGE PublishingTumor Biology1423-03802017-03-013910.1177/1010428317694318Splicing factor hnRNPA2B1 contributes to tumorigenic potential of breast cancer cells through STAT3 and ERK1/2 signaling pathwayYing Hu0Zihan Sun1Jinmu Deng2Baoquan Hu3Wenting Yan4Hongyi Wei5Jun Jiang6Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing, ChinaBreast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing, ChinaDepartment of Mammary Gland and Thyroid Gland, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, ChinaBreast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing, ChinaBreast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing, ChinaBreast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing, ChinaBreast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing, ChinaIncreasing evidence has indicated that the splicing factor hnRNPA2B1 plays a direct role in cancer development, progression, gene expression, and signal transduction. Previous studies have shown that knocking down hnRNPA2B1 in breast cancer cells induces apoptosis, but the mechanism and other functions of hnRNPA2B1 in breast cancer are unknown. The goal of this study was to investigate the biological function, clinical significance, and mechanism of hnRNPA2B1 in breast cancer. The expression of hnRNPA2B1 in 92 breast cancer and adjacent normal tissue pairs was analyzed by immunohistochemical staining. Stable clones exhibiting knockdown of hnRNPA2B1 via small hairpin RNA expression were generated using RNA interference technology in breast cancer cell lines. The effects of hnRNPA2B1 on cell proliferation were examined by MTT and EdU assay, and cellular apoptosis and the cell cycle were examined by flow cytometry. A nude mouse xenograft model was established to elucidate the function of hnRNPA2B1 in tumorigenesis in vivo. The role of hnRNPA2B1 in signaling pathways was investigated in vitro. Our data revealed that hnRNPA2B1 was overexpressed in breast cancer tissue specimens and cell lines. Knockdown of hnRNPA2B1 reduced breast cancer cell proliferation, induced apoptosis, and prolonged the S phase of the cell cycle in vitro. In addition, hnRNPA2B1 knockdown suppressed subcutaneous tumorigenicity in vivo. On a molecular level, hnRNPA2B1 knockdown decreased signal transducer and activator of transcription 3 and extracellular-signal-regulated kinase 1/2 phosphorylation. We concluded that hnRNPA2B1 promotes the tumorigenic potential of breast cancer cells, MCF-7 and MDA-MB-231, through the extracellular-signal-regulated kinase 1/2 or signal transducer and activator of transcription 3 pathway, which may serve as a target for future therapies.https://doi.org/10.1177/1010428317694318
spellingShingle Ying Hu
Zihan Sun
Jinmu Deng
Baoquan Hu
Wenting Yan
Hongyi Wei
Jun Jiang
Splicing factor hnRNPA2B1 contributes to tumorigenic potential of breast cancer cells through STAT3 and ERK1/2 signaling pathway
Tumor Biology
title Splicing factor hnRNPA2B1 contributes to tumorigenic potential of breast cancer cells through STAT3 and ERK1/2 signaling pathway
title_full Splicing factor hnRNPA2B1 contributes to tumorigenic potential of breast cancer cells through STAT3 and ERK1/2 signaling pathway
title_fullStr Splicing factor hnRNPA2B1 contributes to tumorigenic potential of breast cancer cells through STAT3 and ERK1/2 signaling pathway
title_full_unstemmed Splicing factor hnRNPA2B1 contributes to tumorigenic potential of breast cancer cells through STAT3 and ERK1/2 signaling pathway
title_short Splicing factor hnRNPA2B1 contributes to tumorigenic potential of breast cancer cells through STAT3 and ERK1/2 signaling pathway
title_sort splicing factor hnrnpa2b1 contributes to tumorigenic potential of breast cancer cells through stat3 and erk1 2 signaling pathway
url https://doi.org/10.1177/1010428317694318
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