RNA-sequencing-based microRNA (miRNA) expression signatures have revealed that miR-148a-5p (the passenger strand of the miR-148a-duplex) is downregulated in various kinds of cancer tissues. Analysis of The Cancer Genome Atlas (TCGA) database showed that low expression of miR-148a-5p was predictive of a lower survival rate (p = 0.041) in patients with gastric cancer (GC). Downregulation of miR-148a-5p was confirmed in GC clinical specimens, and its ectopic expression attenuated GC cell proliferation. Our search for miRNA target genes identified a total of 18 oncogenic targets of miR-148a-5p in GC cells. Among these targets, high expression levels of six genes (THBS2, P4HA3, SERPINH1, CDH11, BCAT1, and KCNG3) were closely associated with a poor prognosis (10-year survival rates) in GC patients (p < 0.05) according to TCGA database analyses. Furthermore, we focused on SERPINH1 as a chaperone protein involved in collagen folding in humans. Aberrant expression of SERPINH1 (mRNA and protein levels) was confirmed in GC clinical specimens. Knockdown assays of SERPINH1 using siRNAs resulted in inhibition of the aggressive phenotype of GC cells. Exploring the molecular networks controlled by miRNAs (including miRNA passenger strands) will broaden our understanding of the molecular pathogenesis of GC.

基于RNA测序的microRNA（miRNA）表达特征表明，miR-148a-5p（miR- 148a-双链体的过客链）在各种癌症组织中均被下调。癌症基因组图谱（TCGA）数据库的分析表明，miR-148a-5p的低表达可预示 胃癌（GC）患者的生存率较低（p = 0.041）。在GC临床标本中证实了miR-148a-5p的下调，其异位表达减弱了GC细胞的增殖。我们对miRNA靶基因的搜索确定了GC细胞中总共18个miR-148a-5p致癌靶标。在这些靶标中，六个基因（THBS2 根据TCGA数据库分析，P4HA3，SERPINH1，CDH11，BCAT1和KCNG3与GC患者的不良预后（10年生存率）密切相关（p <0.05）。此外，我们专注于SERPINH1作为伴侣蛋白参与人类胶原蛋白的折叠。在GC临床标本中证实了SERPINH1的异常表达（mRNA和蛋白质水平）。使用siRNA进行SERPINH1的基因敲除试验可抑制GC细胞的侵袭性表型。探索由miRNA（包括miRNA乘客链）控制的分子网络将拓宽我们对GC分子发病机理的理解。