Abstract
Gastric cancer (GC) is a common disease globally with high mortality rate. It is therefore necessary to develop novel therapies targeting specific events in the pathogenesis of GC. Some hnRNP family members are involved in multiple cancer biological behaviors. However, the potential function and mechanism of hnRNPR, a new molecule of hnRNP family in GC remains unknown. We found that the expression of hnRNPR was significantly overexpressed in multiple cancers compared to the normal tissues. Functionally, hnRNPR promoted cancer cell proliferation, migration, and invasion. Knockdown of hnRNPR in two type mice models, with two types of tumors models decreased the tumor aggressiveness and metastasis. Mechanistically, hnRNPR targeted oncogenic pathways by stabilizing the expression of CCNB1 and CENPF mRNA level. Knockdown of CCNB1 and CENPF abolished the hnRNPR-induced cell growth and invasion, respectively. Furthermore, the protein level of hnRNPR in the tumor was positively correlated with the expression of CCNB1 and CENPF in clinical samples. Together, these results indicate that overexpression of hnRNPR promoted the aggressiveness of GC by increasing the mRNA expression of CCNB1 and CENPF. HnRNPR-CCNB1/CENPF axis may be a potential therapeutic target for GC treatment.
Highlights
Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related deaths in the world [1]
To the best of our knowledge, many studies have shown that heterogeneous nuclear ribonucleoproteins (hnRNPs) play an important role in tumor progression, the pro-oncogene role of hnRNPR in cancer progression has not been reported
We found that hnRNPR was highly expressed in GC specimens than that in peritumoral control samples by bioinformatic analysis
Summary
Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related deaths in the world [1]. Growing evidence indicates that many RNA-binding proteins are possible cancer biomarkers as they regulate a series of biological processes including tumor initiation, development and drug resistance [6,7,8]. The heterogeneous nuclear ribonucleoproteins (hnRNPs), an RNA-binding protein, can bind to initial transcripts and are involved in all aspects of (pre)mRNA processing including gene transcription, alternative splicing, RNA stabilization, subcellular transport, and degradation control [9,10,11,12]. HnRNPR was originally identified as a component of the hnRNP family It interacts with www.aging-us.com hnRNP complexes to regulate pre-mRNA and mature mRNA transcripts [16]. MiRNAs originate from polyA-tailed primary and precursors (60~70 nucleotides) transcripts that undergo complex and different processing steps until they achieve functional maturity [19]. The function of hnRNPR and the molecular mechanisms in cancer progression are not known
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