PRELIMINARY MIRNA PROFILING IN ERP29-SILENCED TONGUE SQUAMOUS CELL CARCINOMA HIGHLIGHTS CANCER-RELATED PATHWAYS

IF 1.5 Q3 HEMATOLOGY

Hematology, Transfusion and Cell Therapy Pub Date : 2026-03-01 Epub Date: 2026-03-05 DOI:10.1016/j.htct.2026.106280

Bianca Piovesan Melchiori Peruzza, Carmen Silvia Passos Lima, Juliana Carron, Gustavo Jacob Lourenço

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Abstract

Introduction

Head and neck squamous cell carcinoma represent a major global health burden, with tongue tumors being the most common subtype. Endoplasmic reticulum (ER) protein 29 (ERp29) is a chaperone protein, encoded by the ERP29 gene on chromosome 12. It is an ER-resident and its main function is the protein folding and trafficking. Although Erp29 has been implicated in tumor biology, its functional role in tongue squamous cell carcinoma (TSCC) remains poorly understood.

Objective

To identify microRNA (miRNA) alterations and associated signaling pathways induced by ERP29 silencing in TSCC cells.

Materials and methods

SCC-4 TSCC cells (ATCC, CRL-1624) were edited using CRISPR/Cas9 to generate ERP29 knockout clones. miRNA expression was profiled using nCounter® miRNA Expression Assay Kit (NanoString®), normalized to counts-per-million, and analyzed for differential expression versus parental SCC-4 cells. Validated miRNA targets were retrieved from the multiMiR database and subjected to KEGG and Reactome enrichment analyses. All analyses were performed in the R statistical environment.

Results

ERP29 silencing was associated with down-regulation of several miRNAs, including hsa-miR-27b-3p, hsa-miR-30a-5p, hsa-miR-19b-3p, hsa-miR-320e, hsa-miR-378i, and hsa-miR-126-3p, has-miR-1306-5p, has-miR-616-3p (absolute log2 fold-change >8). KEGG analysis revealed strong enrichment of proteoglycans in cancer (hsa05205) and PI3K/AKT signaling (hsa04151), encompassing canonical TSCC drivers such as TP53 (Entrez 7157), PIK3CA (5290), EGFR (1956), HRAS (3265), AKT1 (207), PTEN (5728), and MAPK1/3 (5594/5595). Reactome enrichment highlighted pathways such as signaling by ALK in cancer (HSA-9700206), NOTCH1 signaling (HSA-2644603), and AKT1 E17K activation (HSA-5674400), all related to growth-factor signaling, extracellular matrix remodeling, and immune crosstalk.

Conclusion

These preliminary data from a single TSCC cell line suggest that Erp29 loss could reshape the miRNA landscape and enriches gene networks linked to PI3K/AKT, NOTCH, and proteoglycan-mediated cancer progression. The results are preliminary and require validation in additional cell lines and clinical samples to confirm the role of Erp29 in tumor-host interactions.

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erp29沉默舌鳞状细胞癌的初步mirna分析突出了癌症相关途径

头颈部鳞状细胞癌是全球主要的健康负担，其中舌部肿瘤是最常见的亚型。内质网蛋白29 （ERp29）是一种伴侣蛋白，由12号染色体上的ERp29基因编码。它是er驻留蛋白，其主要功能是蛋白质折叠和转运。尽管Erp29与肿瘤生物学有关，但其在舌鳞状细胞癌（TSCC）中的功能作用仍知之甚少。目的探讨ERP29沉默在TSCC细胞中诱导的microRNA （miRNA）变化及其相关信号通路。材料与方法利用CRISPR/Cas9技术对scc -4 TSCC细胞（ATCC、CRL-1624）进行编辑，生成ERP29基因敲除克隆。使用nCounter®miRNA表达测定试剂盒（NanoString®）分析miRNA表达，归一化为百万分之数，并分析与亲代SCC-4细胞的差异表达。从multiMiR数据库中检索验证的miRNA靶点，并进行KEGG和Reactome富集分析。所有分析均在R统计环境中进行。结果ser29沉默与几种mirna下调相关，包括hsa-miR-27b-3p、hsa-miR-30a-5p、hsa-miR-19b-3p、hsa-miR-320e、hsa-miR-378i和hsa-miR-126-3p、has-miR-1306-5p、has-miR-616-3p（绝对对数2倍变化>；8）。KEGG分析显示，在癌症（hsa05205）和PI3K/AKT信号（hsa04151）中，蛋白聚糖的富集程度较高，包括典型的TSCC驱动因子，如TP53 （Entrez 7157）、PIK3CA（5290）、EGFR（1956）、HRAS（3265）、AKT1（207）、PTEN（5728）和MAPK1/3（5594/5595）。Reactome富集强调了癌症中ALK信号传导（HSA-9700206）、NOTCH1信号传导（HSA-2644603）和AKT1 E17K激活（HSA-5674400）等途径，这些途径都与生长因子信号传导、细胞外基质重塑和免疫串扰有关。这些来自单个TSCC细胞系的初步数据表明，Erp29缺失可以重塑miRNA格局，并丰富与PI3K/AKT、NOTCH和蛋白聚糖介导的癌症进展相关的基因网络。该结果是初步的，需要在其他细胞系和临床样本中验证，以确认Erp29在肿瘤-宿主相互作用中的作用。

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