@Article{or.2026.073080,
AUTHOR = {Yen-Pin Chen, Rathinasamy Baskaran, Hema Sri Devi, Chaouhan Hitesh Singh, Yu-Jung Lin, Marthandam Asokan Shibu, Wei-Wen Kuo, Shih-Chieh Liao, Ming-Cheng Chen, Tso-Fu Wang, Chi-Cheng Li, Tsung-Jung Ho, Tzu-Ching Shih, Shinn-Zong Lin, Chih-Yang Huang},
TITLE = {miR-100-5p Enhances Cell Cycle-Mediated Chemoresistance by Modulating the CTDSPL/pRB/E2F1 Signaling Pathway in Oxaliplatin-Resistant Colorectal Cancer Cells},
JOURNAL = {Oncology Research},
VOLUME = {34},
YEAR = {2026},
NUMBER = {4},
PAGES = {--},
URL = {http://www.techscience.com/or/v34n4/66678},
ISSN = {1555-3906},
ABSTRACT = { <b>Objective:</b> MicroRNAs (miRNAs) are small, non-coding RNAs that play a key role in the development of chemoresistance in various cancer types, including colorectal cancer (CRC). In this study, we aimed to study the underlying mechanisms of miRNA in chemotherapy-resistant CRC. <b>Methods:</b> LoVo CRC cell line was exposed to oxaliplatin at an increased dose, and cells were cultured in the presence of oxaliplatin to develop LoVoOXR cells. Microarray and Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR), western blot, and transwell assay were used to evaluate the chemoresistance in LoVo<sup>OXR</sup> CRC cells. <b>Results:</b> Microarray and qRT-PCR analysis showed an increased expression of miR-100-5p in LoVo<sup>OXR</sup> cells. MTT assay and flow cytometry analysis revealed less apoptosis and higher cell viability in LoVo<sup>OXR</sup> cells. mRNA prediction target gene analysis showed <i>C-terminal domain small phosphatase-like (CTDSPL)</i>, a phosphatase-like tumor suppressor, as a key target of miR-100-5p. CTDSPL expression was low in LoVo<sup>OXR</sup> cells compared to LoVo<sup>WT</sup> cells. miR-100-5p regulates G1/S and S-phase transitions and inhibits differentiation by targeting the CTDSPL/pRB/E2F1 signaling pathway, which involves the modulation of cell cycle effectors in LoVo<sup>OXR</sup> cells. Further, we found that forkhead box P3 (FOXP3), as the upstream target of miR-100-5p, is highly expressed in LoVo<sup>OXR</sup> cells. Inhibiting miR-100-5p and FOXP3 down-regulates miR-100-5p expression, while increased CTDSPL expression contributed to reduced cell proliferation and promoted cell apoptosis in LoVo<sup>OXR</sup> CRC cells. <b>Conclusions:</b> miR-100-5p plays an oncogenic role in inducing chemoresistance through modulation of the CTDSPL/retinoblastoma protein (pRB)/E2F transcription factor 1 (E2F1) axis in CRC cells.},
DOI = {10.32604/or.2026.073080}
}