Prognostic value of OCT4A and SPP1C transcript variant co-expression in early-stage lung adenocarcinoma
Prognostic value of OCT4A and SPP1C transcript variant co-expression in early-stage lung adenocarcinoma
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DOI：
10.1186/s12885-020-06969-0
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发表时间：
2020-06-05
期刊：
影响因子：
3.8
通讯作者：
Ohtsuka, Aiji
中科院分区：
文献类型：
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作者：
Koshimune, Seijiro;Kosaka, Mitsuko;Ohtsuka, Aiji
研究背景八聚体结合转录因子4A（Octamer-binding transcription factor 4A，OCT 4A）是人和小鼠细胞多能性和重编程的重要因子。迄今为止，然而，在体细胞和/或肿瘤tissues.MethodsRT-PCR中的人OCT 4的功能在很大程度上是未知的，用于确定全长剪接形式的OCT 4转录在正常和癌细胞。FLAG标记的OCT 4基因组转基因用于识别OCT 4阳性癌细胞。通过使用启动子驱动的白喉毒素A对OCT 4阳性细胞进行细胞消融，检查了OCT 4在体细胞癌细胞中的潜在作用。OCT 4和分泌磷蛋白1（SPP 1）在早期肺腺癌肿瘤的成绩单进行了分析，并与病理组织学features.ResultsThe结果表明，与鼠细胞，OCT 4A和OCT 4 B的变体转录在人类癌细胞和成人组织，如肺，肾，子宫，乳腺，和眼睛。我们发现OCT 4A和SPP 1C在高度侵袭性的人乳腺癌、子宫内膜癌和肺腺癌细胞系中共表达，但在间皮瘤细胞系中不表达。消融肺腺癌细胞中的OCT 4阳性细胞显著降低细胞迁移和SPP 1C mRNA水平。OCT 4A/SPP 1C轴被发现在原发性，早期，肺腺癌tumors.ConclusionsCo-expression的OCT 4和SPP 1可能与癌症的侵袭性，和OCT 4A/SPP 1C轴可能有助于识别早期肺腺癌的高危患者。与小鼠的情况相反，我们的数据强烈表明OCT 4A和SPP 1C在人类上皮癌的发展和进展中起关键作用。
BackgroundOctamer-binding transcription factor 4A (OCT4A) is essential for cell pluripotency and reprogramming both in humans and mice. To date, however, the function of human OCT4 in somatic and/or tumour tissues is largely unknown.MethodsRT-PCR was used to identify full-length splice forms of OCT4 transcripts in normal and cancer cells. A FLAG-tagged OCT4 genomic transgene was used to identify OCT4-positive cancer cells. A potential role for OCT4 in somatic cancer cells was examined by cell ablation of OCT4-positive cells using promoter-driven diphtheria toxin A. OCT4 and secreted phosphoprotein 1 (SPP1) transcripts in early-stage lung adenocarcinoma tumours were analysed and compared with pathohistological features.ResultsThe results show that, unlike in murine cells, OCT4A and OCT4B variants are transcribed in both human cancer cells and in adult tissues such as lung, kidney, uterus, breast, and eye. We found that OCT4A and SPP1C are co-expressed in highly aggressive human breast, endometrial, and lung adenocarcinoma cell lines, but not in mesothelial tumour cell lines. Ablation of OCT4-positive cells in lung adenocarcinoma cells significantly decreased cell migration and SPP1C mRNA levels. The OCT4A/SPP1C axis was found in primary, early-stage, lung adenocarcinoma tumours.ConclusionsCo-expression of OCT4 and SPP1 may correlate with cancer aggressiveness, and the OCT4A/SPP1C axis may help identify early-stage high-risk patients with lung adenocarcinoma. Contrary to the case in mice, our data strongly suggest a critical role for OCT4A and SPP1C in the development and progression of human epithelial cancers.