Comprehensive long-read transcriptomic analysis reveals multi-level transcriptional alterations mediated by miR-214-3p dysregulation in gastric cancer cells

TL;DR

This study uses long-read sequencing to show how miR-214-3p affects gene expression, splicing, and cancer cell behavior in gastric cancer.

Contribution

The study reveals miR-214-3p's multi-level transcriptional effects, including splicing and polyadenylation changes, in gastric cancer cells.

Findings

miR-214-3p alters gene expression related to apoptosis and transcriptional regulation.

It influences alternative splicing of hundreds of genes linked to cell division and senescence.

miR-214-3p overexpression promotes cancer cell proliferation and inhibits apoptosis.

Abstract

Gastric cancer remains one of the leading causes of cancer-related death worldwide. miR-214-3p, a microRNA, has been reported to exhibit dysregulated expression and play important regulatory roles in various cancers. However, the global targets and underlying mechanisms of miR-214-3p in gastric cancer progression remain poorly understood.

In this study, we performed long-read transcriptomic sequencing to comprehensively characterize transcriptome-wide variations in AGS gastric cancer cells following miR-214-3p overexpression (OE) or knockdown (KD). Functional in vitro experiments were conducted to validate the newly identified transcripts and assess the effects of miR-214-3p OE on cell proliferation and apoptosis in AGS cells.

Our results demonstrated that miR-214-3p OE and KD significantly altered the expression levels of numerous genes at both transcript and gene levels, particularly those involved in apoptosis and transcriptional regulation. Interestingly, miR-214-3p KD and OE showed consistent directional effects on the expression of some target genes. Additionally, miR-214-3p broadly influenced the alternative splicing of hundreds of genes, including those associated with cell division, senescence, and transcriptional regulation. Notably, changes in miR-214-3p expression also affected the alternative polyadenylation and 3’UTR lengths of transcripts. Furthermore, our in vitro experiments revealed that miR-214-3p OE significantly promoted the proliferation of AGS cells and inhibited apoptosis, suggesting its potential oncogenic role.

Collectively, these findings highlight the potential multifaceted regulatory roles of miR-214-3p in mediating proliferation and apoptosis through diverse mechanisms in AGS gastric cancer cells, thereby advancing our understanding of its critical role in gastric cancer progression and its therapeutic potential.

The online version contains supplementary material available at 10.1186/s12885-025-15323-1.

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