Transmembrane protein 98 (TMEM98) is a recently discovered gene, the inhibition of which has preliminarily been demonstrated to inhibit progression of several solid cancers in vitro. However, its involvement in tumorigenesis of gastric cancer (GC) has not been reported. Here, we aimed to explore the expression of TMEM98 in GC tissues and cell lines and to determine the role of TMEM98 in GC cell proliferation and invasion. TMEM98 was significantly upregulated in GC tissues, which was associated with low survival rate of GC patients. Interestingly, GC cell proliferation and invasion were promoted by TMEM98 messenger RNA (mRNA) upregulation and inhibited by TMEM98 mRNA downregulation, but not affected by TMEM98 protein. Using RNA‐binding protein immunoprecipitation assay and RNA pull‐down assay, we demonstrated that TMEM98 mRNA could directly bind with and upregulate nuclear factor 90 (NF90). Similarly, NF90 protein could not only enhance the stability of TMEM98 mRNA but antagonize the suppressive effect of TMEM98‐small interfering RNA on proliferation and invasion in MKN‐45 cells. Moreover, RNA pull‐down assay, with wild‐type (WT) and binding‐site‐mutated biotinylated TMEM98 mRNA transcripts, demonstrated that WT TMEM98 mRNA bound with NF90 protein through an 8‐nt motif at the last exon, but the motif mutation abolished the capacity of TMEM98 mRNA binding to NF90 protein. Furthermore, overexpression of the WT last exon of TMEM98 increased NF90 expression and cell proliferation/invasion expectedly, but overexpression of the mutated last exon had no obvious effect. In conclusion, TMEM98 mRNA enhanced the proliferation and invasion of GC cells by interacting with the NF90 protein.

中文翻译：

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TMEM98 mRNA通过与NF90蛋白直接相互作用来促进胃细胞的增殖和侵袭。

跨膜蛋白98（TMEM98）是最近发现的基因，已初步证明其抑制作用可在体外抑制几种实体癌的进展。然而，尚未报道其参与胃癌（GC）的肿瘤发生。在这里，我们旨在探索TMEM98在GC组织和细胞系中的表达，并确定TMEM98在GC细胞增殖和侵袭中的作用。TMEM98在GC组织中显着上调，这与GC患者的低存活率有关。有趣的是，TMEM98信使RNA（mRNA）上调促进了GC细胞的增殖和侵袭，而TMEM98 mRNA的下调抑制了GC细胞的增殖和侵袭，但不受TMEM98蛋白的影响。使用RNA结合蛋白免疫沉淀测定法和RNA下拉测定法，我们证明TMEM98 mRNA可以直接结合并上调核因子90（NF90）。同样，NF90蛋白不仅可以增强TMEM98 mRNA的稳定性，而且可以拮抗TMEM98-小分子干扰RNA对MKN-45细胞增殖和侵袭的抑制作用。此外，RNA下拉测定法具有野生型（WT）和结合位点突变的生物素化TMEM98 mRNA转录本，证明WT TMEM98 mRNA与NF90蛋白通过最后一个外显子的8nt基序结合，但基序突变消除了TMEM98 mRNA与NF90蛋白结合的能力。此外，TMEM98 WT的最后一个外显子的过表达预期会增加NF90表达和细胞增殖/侵袭，但突变的最后一个外显子的过表达没有明显的作用。结论，