Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565‑0871, Japan.
Int J Oncol. 2019 Mar;54(3):1001-1009. doi: 10.3892/ijo.2019.4678. Epub 2019 Jan 7.
Polymerase (Pol) III‑dependent transcription controls the abundance of transfer RNAs, 5S ribosomal RNA and small non‑coding RNAs within cells, and is known to serve an essential role in the maintenance of intracellular homeostasis. However, its contribution to cancer progression has not been extensively explored. The present study demonstrated that the evolutionarily conserved MAF1 homolog, negative regulator of RNA Pol III (MAF1) may be closely associated with malignant potential and poor prognosis in colorectal cancer (CRC). Notably, immunohistochemical analysis of 146 CRC surgical specimens revealed that high expression levels of MAF1 were associated with advanced tumor depth, lymph node metastasis, distant metastasis and poor prognosis. In vitro loss‑of‑function assays revealed that MAF1 knockdown suppressed chemoresistance and migration of CRC cancer cells. Furthermore, detailed analysis of an independent CRC dataset (n=615) demonstrated that the prognostic impact of MAF1 gene expression was particularly marked in microsatellite instability (MSI)‑positive patients, who benefit from immune checkpoint blockade. High expression levels of MAF1 were revealed to be an independent prognostic indicator in MSI‑positive CRC. These findings suggested that MAF1 may have an essential role in CRC progression, particularly in MSI‑positive cases.
聚合酶（Pol）III 依赖性转录控制细胞内转移 RNA、5S 核糖体 RNA 和小非编码 RNA 的丰度，已知其在维持细胞内平衡中起着至关重要的作用。然而，其在癌症进展中的作用尚未得到广泛探索。本研究表明，进化上保守的 MAF1 同源物，RNA Pol III 的负调节剂（MAF1）可能与结直肠癌（CRC）的恶性潜能和不良预后密切相关。值得注意的是，对 146 例 CRC 手术标本的免疫组织化学分析表明，MAF1 的高表达水平与肿瘤深度进展、淋巴结转移、远处转移和不良预后相关。体外功能丧失实验表明，MAF1 敲低可抑制 CRC 癌细胞的化疗耐药性和迁移。此外，对独立 CRC 数据集（n=615）的详细分析表明，MAF1 基因表达的预后影响在微卫星不稳定（MSI）阳性患者中尤为显著，这些患者受益于免疫检查点阻断。MAF1 的高表达水平被揭示是 MSI 阳性 CRC 的独立预后指标。这些发现表明，MAF1 可能在 CRC 进展中具有重要作用，特别是在 MSI 阳性病例中。
