Liu Qiang, Shen Hongliang, Naguib Andrew, Weiss Robert M, Martin Darryl T
Department of Urology, Yale University School of Medicine, New Haven, CT, USA.
Department of Urology, Renji Hospital Affiliated To Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Mol Biomed. 2021 Oct 10;2(1):31. doi: 10.1186/s43556-021-00053-0.
Prostate cancer is the most common solid organ malignancy in the United States, and has the highest probability of all cancers in becoming invasive. New molecular targets are needed to define and impede the growth and progression of advanced prostate cancers. Claudins (Cldns) are transmembrane proteins that regulate paracellular permeability and cell polarity, and their levels are elevated in many human cancers such as breast, ovarian, pancreatic, and prostatic cancers. Previously, we found that Cldn3 and Cldn4 are expressed in aggressive high-grade human prostate cancer specimens. We and others have shown that there are higher levels of Cldn3 and Cldn4 in metastatic human prostate cancer cells than in normal human prostate cells. The result of targeting Cldn3 and Cldn4 expression on the growth and viability of prostate cancer cells has not been elucidated. Human prostate cancer PC3 and LNCaP cells were transfected with Cldn3 or -4 small interfering RNAs (siRNAs). Cldn3/Cldn4 siRNA treatment resulted in a greater than 85% decrease in the protein levels of Cldn3 and Cldn4, which was accompanied by a 30-40% decrease in prostate cancer cell growth and a 60-65% reduction in cell viability. There was decreased cell migration with Cldn3 and Cldn4 siRNA in both PC3 and LNCaP cells and a 60-75% decrease in the number of clones when treated with siCldn3 or siCldn4 compared to control. Knocking down Cldn3/Cldn4 affects prostate cancer cell growth and survival and may have therapeutic implications.
前列腺癌是美国最常见的实体器官恶性肿瘤，在所有癌症中发生侵袭的可能性最高。需要新的分子靶点来界定和阻止晚期前列腺癌的生长和进展。紧密连接蛋白（Claudins，Cldns）是调节细胞旁通透性和细胞极性的跨膜蛋白，其水平在许多人类癌症中升高，如乳腺癌、卵巢癌、胰腺癌和前列腺癌。此前，我们发现Cldn3和Cldn4在侵袭性高级别人类前列腺癌标本中表达。我们和其他人已经表明，转移性人类前列腺癌细胞中Cldn3和Cldn4的水平高于正常人类前列腺细胞。针对Cldn3和Cldn4表达对前列腺癌细胞生长和活力的影响尚未阐明。用Cldn3或-4小干扰RNA（siRNAs）转染人类前列腺癌PC3和LNCaP细胞。Cldn3/Cldn4 siRNA处理导致Cldn3和Cldn4的蛋白水平降低超过85%，同时前列腺癌细胞生长减少30-40%，细胞活力降低60-65%。在PC3和LNCaP细胞中，Cldn3和Cldn4 siRNA均使细胞迁移减少，与对照组相比，用siCldn3或siCldn4处理时克隆数减少60-75%。敲低Cldn3/Cldn4会影响前列腺癌细胞的生长和存活，可能具有治疗意义。
