Chen Chiachen, Lan Michael S
Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Biology (Basel). 2022 Sep 20;11(10):1376. doi: 10.3390/biology11101376.
An aggressive form of neuroblastoma (NB), a malignant childhood cancer derived from granule neuron precursors and sympathoadrenal lineage, frequently comprises amplification/elevated N-Myc expression, which contributes to the development of neural crest-derived embryonal malignancy. N-Myc is an oncogenic driver in NB. Persistent N-Myc expression during the maturation of SA precursor cells can cause blockage of the apoptosis and induce abnormal proliferation, resulting in NB development. An insulinoma-associated-1 (INSM1) zinc-finger transcription factor has emerged as an NB biomarker that plays a critical role in facilitating tumor cell growth and transformation. INSM1 plays an essential role in sympathoadrenal cell differentiation. N-Myc activates endogenous INSM1 through an of the proximal promoter, whereas INSM1 enhances N-Myc stability via RAC-α-serine/threonine protein kinase (AKT) phosphorylation in NB. The ectopic expression of INSM1 stimulates NB tumor growth in contrast to the knockdown of INSM1 that inhibits NB cell proliferation. The clinical pathological result and bioinformatics analysis show that INSM1 is a strong diagnostic and a prognostic biomarker for the evaluation of NB progression. The INSM1/N-Myc expression shows high clinical relevance in NB. Therefore, targeting the INSM1/N-Myc-associated signaling axis should be a feasible approach to identifying new drugs for the suppression of NB tumor growth.
神经母细胞瘤（NB）是一种侵袭性的儿童恶性肿瘤，起源于颗粒神经元前体和交感肾上腺谱系，常伴有N-Myc基因扩增/表达升高，这促使神经嵴来源的胚胎性恶性肿瘤发展。N-Myc是NB中的致癌驱动因子。在交感肾上腺（SA）前体细胞成熟过程中持续的N-Myc表达可导致细胞凋亡受阻并诱导异常增殖，从而引发NB。胰岛素瘤相关蛋白1（INSM1）锌指转录因子已成为一种NB生物标志物，在促进肿瘤细胞生长和转化中起关键作用。INSM1在交感肾上腺细胞分化中起重要作用。N-Myc通过近端启动子的 激活内源性INSM1，而在NB中INSM1通过RAC-α-丝氨酸/苏氨酸蛋白激酶（AKT）磷酸化增强N-Myc的稳定性。与抑制NB细胞增殖的INSM1敲低相反，INSM1的异位表达刺激NB肿瘤生长。临床病理结果和生物信息学分析表明，INSM1是评估NB进展的强有力的诊断和预后生物标志物。INSM1/N-Myc表达在NB中显示出高度的临床相关性。因此，靶向INSM1/N-Myc相关信号轴应该是一种可行的方法来确定抑制NB肿瘤生长的新药。 （注：原文中“An insulinoma-associated-1 (INSM1) zinc-finger transcription factor has emerged as an NB biomarker that plays a critical role in facilitating tumor cell growth and transformation.”一句中“through an of the proximal promoter”部分缺失关键信息，翻译可能存在不准确之处。）
