TY - JOUR
T1 - Decoding oncogenic secrets of regulator of chromosome condensation 1: A breakthrough mechanistic evidence from breast and lung cancer models
AU - El-Tanani, Mohamed
AU - Satyam, Shakta Mani
AU - Rabbani, Syed Arman
AU - Obeidat, Razan M
AU - El-Tanani, Yahia
AU - Aljabali, Alaa A A
AU - Hatahet, Taher
PY - 2025/3/31
Y1 - 2025/3/31
N2 - The Regulator of Chromosome Condensation 1 (RCC1), a master regulator of cell cycle progression, chromatin structure, and nuclear transport, emerges as a powerful driver of cancer progression. Elevated RCC1 expression in breast and lung cancers is closely tied to enhanced tumor cell survival, proliferation, and metastasis, positioning it as a promising therapeutic target. This study unveils RCC1's pivotal role in cancer biology by silencing its expression in MDA-MB-231 (breast cancer) and A549 (lung cancer) cell lines using shRNA. RCC1 knockdown dramatically reduced cell viability, colony formation, and motility, while inducing apoptosis, as evidenced by increased apoptotic markers and reduced anti-apoptotic Bcl2 expression. Gene expression analysis revealed downregulation of cell cycle and DNA repair pathways, highlighting RCC1's critical role in sustaining oncogenic mechanisms. These findings underscore RCC1 as a gatekeeper of tumor survival, capable of resisting apoptosis and promoting metastasis. Targeting RCC1 offers a dual advantage: disrupting cancer growth and enhancing apoptotic pathways, creating an exciting opportunity for precision therapies. By illuminating RCC1's integration into survival networks, this study not only advances our understanding of cancer biology but also lays the groundwork for innovative treatments aimed at halting cancer progression and metastasis.
AB - The Regulator of Chromosome Condensation 1 (RCC1), a master regulator of cell cycle progression, chromatin structure, and nuclear transport, emerges as a powerful driver of cancer progression. Elevated RCC1 expression in breast and lung cancers is closely tied to enhanced tumor cell survival, proliferation, and metastasis, positioning it as a promising therapeutic target. This study unveils RCC1's pivotal role in cancer biology by silencing its expression in MDA-MB-231 (breast cancer) and A549 (lung cancer) cell lines using shRNA. RCC1 knockdown dramatically reduced cell viability, colony formation, and motility, while inducing apoptosis, as evidenced by increased apoptotic markers and reduced anti-apoptotic Bcl2 expression. Gene expression analysis revealed downregulation of cell cycle and DNA repair pathways, highlighting RCC1's critical role in sustaining oncogenic mechanisms. These findings underscore RCC1 as a gatekeeper of tumor survival, capable of resisting apoptosis and promoting metastasis. Targeting RCC1 offers a dual advantage: disrupting cancer growth and enhancing apoptotic pathways, creating an exciting opportunity for precision therapies. By illuminating RCC1's integration into survival networks, this study not only advances our understanding of cancer biology but also lays the groundwork for innovative treatments aimed at halting cancer progression and metastasis.
KW - guanine nucleotide Exchange Factors - metabolism - genetics
KW - apoptosis - genetics
KW - female
KW - cell proliferation - genetics
KW - cell survival - genetics
KW - A549 Cells
KW - Lung Neoplasms - genetics - pathology - metabolism
KW - nuclear Proteins - metabolism - genetics
KW - humans
KW - breast neoplasms - genetics - pathology - metabolism
KW - Cell Movement - genetics
KW - cell line
KW - tumor
KW - gene expression regulation
KW - Neoplastic
KW - Cell Cycle Proteins - metabolism - genetics
KW - Cell Movement/genetics
KW - Cell Proliferation
KW - Humans
KW - Gene Expression Regulation, Neoplastic
KW - Cell Survival/genetics
KW - Lung Neoplasms/genetics
KW - Female
KW - Nuclear Proteins/genetics
KW - Guanine Nucleotide Exchange Factors/genetics
KW - Apoptosis/genetics
KW - Cell Line, Tumor
KW - Breast Neoplasms/genetics
KW - Cell Cycle Proteins/genetics
U2 - 10.1371/journal.pone.0319748
DO - 10.1371/journal.pone.0319748
M3 - Article
C2 - 40163507
SN - 1932-6203
VL - 20
SP - e0319748
JO - PLoS ONE
JF - PLoS ONE
IS - 3
ER -