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Updated: Aug 30, 2025

Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
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An Alternatively Spliced p62 Isoform Confers Resistance to Chemotherapy in Breast Cancer

Qianying Guo1, Hao Wang1, Jiahao Duan2

  • 1Department of Pathology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, P.R. China.

Cancer Research
|August 30, 2022
PubMed

Insights

A novel p62 mRNA isoform (p62-SU) with a short 3' untranslated region promotes breast cancer chemoresistance. This isoform evades microRNA repression, leading to increased p62 protein and reduced treatment sensitivity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Chemotherapy resistance is a significant challenge in breast cancer treatment.
  • A majority of patients undergoing neoadjuvant chemotherapy (NAC) do not achieve a complete pathologic response.

Purpose of the Study:

  • To identify novel mechanisms driving chemoresistance in breast cancer.
  • To investigate the role of p62 mRNA isoforms in breast cancer treatment response.

Main Methods:

  • RNA sequencing, qRT-PCR, 3'-RACE, and Northern blot analysis were used to identify and characterize p62 mRNA isoforms.
  • In vitro and in vivo experiments assessed the functional impact of p62 isoforms on breast cancer cell behavior.
  • Mechanistic studies explored the roles of CPSF1 and miR-124-3p in regulating p62 expression.

Main Results:

  • A novel p62 mRNA isoform with a short 3 untranslated region (p62-SU) was identified and associated with chemoresistance.
  • Ectopic expression of p62-SU enhanced breast cancer cell proliferation, migration, invasion, and chemoresistance.
  • CPSF1-mediated alternative polyadenylation and escape from miR-124-3p repression led to increased p62-SU protein levels.

Conclusions:

  • A CPSF1-p62-miR-124-3p signaling axis contributes to breast cancer chemoresistance.
  • The p62-SU isoform represents a potential therapeutic target for overcoming treatment resistance in breast cancer.

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