Trehan Deepika, Kumari Ranbala, Sharma Jyoti, Satuluri Sri Harsha, Sahay Satya, Jha Nitu Kumari, Batra Janendra K, Agrawal Usha
ICMR-National Institute of Pathology New Delhi, India.
Jamia Hamdard University New Delhi, India.
Am J Cancer Res. 2023 Aug 15;13(8):3832-3852. eCollection 2023.
Protein kinase C (PRKC) isozymes activate many signaling pathways and promote tumorigenesis, which can be confirmed by masking the kinase activity. In the present study, the kinase activity of PRKC ε and ζ isozymes was masked by siRNA in bladder cancer, and the consequent gene profile was evaluated. Here, we show that the commonly dysregulated genes affected by both the isozymes were the chemokines (CXCL8 & CXCL10), adhesion molecules (ICAM1, SPP1, MMP3, VEGFA) and mutated isoform of TP53. As these same genes were upregulated in bladder cancer patients, the activity of the kinase in downregulating them is confirmed. These genes are associated with regulating the tumor microenvironment, proliferation and differentiation of cancer cells and poor prognosis. The effect of kinase masking in downregulating these genes in bladder cancer indicates the benefits PRKC inhibitors may have in managing these patients.
蛋白激酶C（PRKC）同工酶激活许多信号通路并促进肿瘤发生，这可以通过掩盖激酶活性来证实。在本研究中，PRKCε和ζ同工酶的激酶活性在膀胱癌中被小干扰RNA（siRNA）掩盖，并对由此产生的基因谱进行了评估。在此，我们表明，受这两种同工酶共同影响而失调的常见基因是趋化因子（CXCL8和CXCL10）、黏附分子（ICAM1、SPP1、MMP3、VEGFA）和TP53的突变异构体。由于这些相同的基因在膀胱癌患者中上调，因此证实了激酶在下调它们方面的活性。这些基因与调节肿瘤微环境、癌细胞的增殖和分化以及不良预后有关。在膀胱癌中激酶掩盖对下调这些基因的作用表明PRKC抑制剂在治疗这些患者中可能具有的益处。
