Silencing hnRNPD inhibits gastric cancer growth by increasing TXNIP-mediated oxidative stress.

[BACKGROUND] RNA-binding proteins (RBPs) are essential for controlling gene expression, and their dysregulation is a key factor in tumor development and progression. Heterogeneous nuclear ribonucleoprotein D (hnRNPD), a member of the hnRNP family of RBPs, is aberrantly expressed in various tumors. However, its role and underlying mechanisms in gastric cancer have not been determined.

[METHODS] The expression patterns of hnRNPD in gastric cancer were analyzed using publicly available datasets and clinical specimens. The effects of hnRNPD on gastric cancer cell growth were assessed using the Cell Counting Kit-8 (CCK-8) and colony formation assays. Target genes regulated by hnRNPD were identified through RNA sequencing (RNA-seq) and RNA immunoprecipitation sequencing (RIP-seq).

[RESULTS] Elevated expression of hnRNPD was observed in gastric cancer, and this overexpression was associated with an unfavorable prognosis. Knocking down hnRNPD could suppress the growth of gastric cancer cells and enhance endogenous oxidative stress. Thioredoxin-interacting protein (TXNIP) was identified as a downstream target of hnRNPD. Further analysis confirmed that hnRNPD diminished TXNIP expression by binding to and destabilizing its mRNA. Moreover, silencing TXNIP reversed the decrease in cell growth and the increase in oxidative stress caused by hnRNPD knockdown.

[CONCLUSION] Our study highlights hnRNPD as a major contributor to gastric carcinogenesis. The knockdown of hnRNPD hinders gastric cancer growth by directly interacting with TXNIP, promoting its expression, and inducing oxidative stress. These findings suggest that hnRNPD may serve as a valuable target for the treatment of gastric cancer.