1 Citation (Scopus)

Abstract

Our recent studies have indicated that specificity protein-1 (Sp1) accumulates substantially in the early stage of lung cancer but is partially decreased in the late stages, which is an important factor in the progression of the cancer. In this study, we found that Nm23-H1 and hnRNPA2/B1 could be recruited to the 5′UTR of Sp1 mRNA. In investigating the clinical relevance of Nm23-H1/Sp1 levels, we found a positive correlation between lung cancer patients with poor prognosis and low levels of Sp1 and Nm23-H1, suggesting an association between Nm23-H1/Sp1 levels and survival rate. Knockdown of Nm23-H1 inhibits lung cancer growth but increases lung cancer cell malignancy, which could be rescued by overexpression of Sp1, indicating that Nm23-H1-induced Sp1 expression is critical for lung cancer progression. We also found that Nm23-H1 increases the protein stability of hnRNPA2/B1and is thereby co-recruited to the 5′UTR of Sp1 mRNA to regulate cap-independent translational activity. Since the Sp1 level is tightly regulated during lung cancer progression, understanding the molecular mechanisms underlying the regulation by Nm23-H1/hnRNPA2B1 of Sp1 expression in the various stages of lung cancer will be beneficial for lung cancer therapy in the future.

Original languageEnglish
Article number9166
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

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Protein Biosynthesis
Lung Neoplasms
Proteins
Messenger RNA
Protein Stability
Neoplasms
Survival Rate

ASJC Scopus subject areas

  • General

Cite this

Nm23-H1-stabilized hnRNPA2/B1 promotes internal ribosomal entry site (IRES)-mediated translation of Sp1 in the lung cancer progression. / Hung, Chia Yang; Wang, Yi Chang; Chuang, Jian Ying; Young, Ming Jer; Liaw, Hungjiun; Chang, Wen Chang; Hung, Jan Jong.

In: Scientific Reports, Vol. 7, No. 1, 9166, 01.12.2017.

Research output: Contribution to journalArticle

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abstract = "Our recent studies have indicated that specificity protein-1 (Sp1) accumulates substantially in the early stage of lung cancer but is partially decreased in the late stages, which is an important factor in the progression of the cancer. In this study, we found that Nm23-H1 and hnRNPA2/B1 could be recruited to the 5′UTR of Sp1 mRNA. In investigating the clinical relevance of Nm23-H1/Sp1 levels, we found a positive correlation between lung cancer patients with poor prognosis and low levels of Sp1 and Nm23-H1, suggesting an association between Nm23-H1/Sp1 levels and survival rate. Knockdown of Nm23-H1 inhibits lung cancer growth but increases lung cancer cell malignancy, which could be rescued by overexpression of Sp1, indicating that Nm23-H1-induced Sp1 expression is critical for lung cancer progression. We also found that Nm23-H1 increases the protein stability of hnRNPA2/B1and is thereby co-recruited to the 5′UTR of Sp1 mRNA to regulate cap-independent translational activity. Since the Sp1 level is tightly regulated during lung cancer progression, understanding the molecular mechanisms underlying the regulation by Nm23-H1/hnRNPA2B1 of Sp1 expression in the various stages of lung cancer will be beneficial for lung cancer therapy in the future.",
author = "Hung, {Chia Yang} and Wang, {Yi Chang} and Chuang, {Jian Ying} and Young, {Ming Jer} and Hungjiun Liaw and Chang, {Wen Chang} and Hung, {Jan Jong}",
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AU - Chuang, Jian Ying

AU - Young, Ming Jer

AU - Liaw, Hungjiun

AU - Chang, Wen Chang

AU - Hung, Jan Jong

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