Matsuoka Izumi, Kasai Takahiro, Onaga Chotaro, Ozaki Ayaka, Motomura Hitomi, Maemura Yuki, Tada Yuna, Mori Haruka, Hara Yasushi, Xiong Yuyun, Sato Keiko, Tamori Shoma, Sasaki Kazunori, Ohno Shigeo, Akimoto Kazunori
Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
Oncol Lett. 2024 Jul 5;28(3):426. doi: 10.3892/ol.2024.14558. eCollection 2024 Sep.
Solute carrier family 20 member 1 (SLC20A1) is a sodium/inorganic phosphate symporter, which has been identified as a prognostic marker in several types of cancer, including pancreatic cancer. However, to the best of our knowledge, the association between expression and cancer stem cell (CSC) markers, such as aldehyde dehydrogenase 1 (ALDH1), in pancreatic ductal adenocarcinoma (PDAC), and the role of in PDAC CSCs remains unclear. In the present study, a genomic dataset of primary pancreatic cancer (The Cancer Genome Atlas, Pan-Cancer Atlas) was downloaded and analyzed. Kaplan-Meier analysis and multivariate Cox regression analysis were performed to evaluate the overall survival, disease-specific survival (DSS), disease-free interval (DFI) and progression-free interval (PFI). Subsequently, small interfering RNA (siRNA) knockdown (KD) was induced in the PANC-1 and MIA-PaCa-2 PDAC cell lines, and in sorted high ALDH1 activity (ALDH1) cells, after which, cell viability, tumor sphere formation, cell death and caspase-3 activity were examined. The results revealed that patients with high expression of ( ) at tumor stage I had a poor prognosis compared with patients with low expression of ( ) in terms of DSS, DFI and PFI. In addition, patients with high expression of and ( ) exhibited poorer clinical outcomes than patients with high expression of and low expression of ( ), low expression of and high expression of ( ) and . siRNA KD in ALDH1 cells isolated from PANC-1 and MIA-PaCa-2 cell lines resulted in suppression of tumorsphere formation, and enhancement of cell death and caspase-3 activity. These results suggested that was involved in cell survival via the suppression of caspase-3-dependent apoptosis, and contributed to cancer progression and poor clinical outcomes in PDAC. In conclusion, may be used as a prognostic marker and novel therapeutic target of ALDH1-positive pancreatic CSCs.
溶质载体家族20成员1(SLC20A1)是一种钠/无机磷酸盐同向转运体,已被确定为包括胰腺癌在内的多种癌症的预后标志物。然而,据我们所知,在胰腺导管腺癌(PDAC)中,其表达与癌症干细胞(CSC)标志物(如醛脱氢酶1(ALDH1))之间的关联以及其在PDAC CSCs中的作用仍不清楚。在本研究中,下载并分析了原发性胰腺癌的基因组数据集(癌症基因组图谱,泛癌图谱)。进行了Kaplan-Meier分析和多变量Cox回归分析,以评估总生存期、疾病特异性生存期(DSS)、无病间期(DFI)和无进展生存期(PFI)。随后,在PANC-1和MIA-PaCa-2 PDAC细胞系以及分选的高ALDH1活性(ALDH1)细胞中诱导小干扰RNA(siRNA)敲低(KD),之后检测细胞活力、肿瘤球形成、细胞死亡和半胱天冬酶-3活性。结果显示,在肿瘤I期,高表达( )的患者与低表达( )的患者相比,在DSS、DFI和PFI方面预后较差。此外,高表达 且高表达 ( )的患者比高表达 且低表达 ( )、低表达 且高表达 ( )以及 的患者表现出更差的临床结局。从PANC-1和MIA-PaCa-2细胞系分离的ALDH1细胞中的siRNA KD导致肿瘤球形成受到抑制,细胞死亡和半胱天冬酶-3活性增强。这些结果表明, 通过抑制半胱天冬酶-3依赖性凋亡参与细胞存活,并促成PDAC中的癌症进展和不良临床结局。总之, 可作为ALDH1阳性胰腺CSCs的预后标志物和新型治疗靶点。