Data from An Alternatively Spliced p62 Isoform Confers Resistance to Chemotherapy in Breast Cancer

• DOI: 10.1158/0008-5472.c.6514242
• Publication Date: 2024-03-12T22:46:07Z
• Authors: Qianying Guo; Hao Wang; Jiahao Duan; Wenwu Luo; Rongrong Zhao; Yuting Shen; Bijun Wang; Siqi Tao; Yi Sun; Qian Ye; Xiaomin Bi; Hui Yuan; Qiang Wu; Peter E. Lobie; Tao Zhu; Sheng Tan; Xing Huang; Zhengsheng Wu

<div>Abstract<p>Resistance to chemotherapy remains a major obstacle the successful treatment of breast cancer. More than 80% patients who receive neoadjuvant (NAC) do not achieve pathologic complete response. In this study, we report novel p62 mRNA isoform with short 3′-UTR (untranslated region; p62-SU, 662-nt) that is associated chemoresistance in cancer cells and tissue specimens. The was identified by RNA sequencing qRT-PCR, 3′-RACE, Northern blot analysis. <i>In vitro</i> <i>in vivo</i>, ectopic expression p62-SU promoted cell proliferation, migration, invasion, compared full-length (p62-LU, 1,485-nt). Mechanistically, cleavage polyadenylation specific factor 1 (CPSF1) modulated through alternative polyadenylation. addition, escaped miR-124-3p–mediated repression upregulated protein expression, thereby inducing p62-dependent chemoresistance. These data suggest CPSF1-p62-miR-124-3p signaling axis responsible for reduced sensitivity chemotherapy.</p>Significance:<p>Resistance NAC driven escapes miRNA-mediated leads increased expression.</p></div>