Amplifying colorectal cancer progression - impact of a PDIA4/SP1 positive feedback loop by circPDIA4 sponging miR-9-5p

Sep 21, 2026

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Objective: Colorectal cancer (CRC) is a prevalent malignant tumor with high fatality. CircPDIA4 has been implicated in cancer development as a facilitator, yet the role of the circPDIA4/miR-9-5p/SP1 axis in CRC development remains unclear. Methods: Western blot, immunohistochemistry, and RT-qPCR assessed gene expression; CCK-8 evaluated growth; Transwell assessed invasion and migration; luciferase reporter and RIP tested molecular binding; in vivo assays measured tumor growth. Results and conclusions support circPDIA4-driven feedback as a driver worsening CRC progression and suggesting a ceRNA biomarker for therapy.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages18

Reading Time45 min

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Abstract

Methods and assays

Results

Conclusions

Introduction

Clinical burden of colorectal cancer

Endoplasmic reticulum stress and PDI family

Oncogenic circRNAs derived from PDI family

Cancer Biol Med 2024. doi: 10.20892/j.issn.2095-3941.2024.0112 ORIGINAL ARTICLE Amplifying colorectal cancer progression: impact of a PDIA4/ SP1 positive feedback loop by circPDIA4 sponging miR-9-5p Yan Zhuang1*, Yiding Ai2*, Peng Li3, Xin Yue1, Yue Li4, Luling Shan4, Tongtong Wang4, Peng Zhao4, Xun Jin2 1 Department of Colorectal Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin 300060, China; 2 Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin 300060, China; 3 Department of Neurosurgery and Neuro-Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin 300060, China; 4 Department of Gastro Colorectal Oncology, Tianjin Cancer Hospital Airport Hospital, Tianjin 300308, China | ABSTRACT | Objective: Colorectal cancer (CRC) is a prevalent malignant tumor with a high fatality rate. CircPDIA4 has been shown to have a vital role in cancer development by acting as a facilitator. Nevertheless, the impact of the circPDIA4/miR-9-5p/SP1 axis on development of CRC has not been studied. | | --- | --- | | KEYWORDS | Methods: Western blot, immunohistochemistry, and reverse transcription-quantitative polymerase chain reaction assays were used to analyze gene expression. The CCK-8 assay was used to assess cell growth. The Transwell assay was used to detect invasion and migration of cells. The luciferase reporter and RNA immunoprecipitation tests were used to determine if miR-9-5p and circPDIA4 (or SP1) bind to one another. An in vivo assay was used to measure tumor growth.
Results: It was shown that circPDIA4 expression was greater in CRC cell lines and tissues than healthy cell lines and tissues. CircPDIA4 knockdown prevented the invasion, migration, and proliferation of cells in CRC. Additionally, the combination of circPDIA4 and miR-9-5p was confirmed, as well as miR-9-5p binding to SP1 . Rescue experiments also showed that the circPDIA4/miR-9-5p/SP1 axis accelerated the development ofCRC. In addition, SP1 combined with the promoter region ofcircPDIA4 and induced circPDIA4 transcription. CircPDIA4 was shown to facilitate tumor growth in an in vivo assay.
Conclusions: The circPDIA4/miR-9-5p/SP1 feedback loop was shown to aggravate CRC progression. This finding suggests that the ceRNA axis may be a promising biomarker for CRC patient treatment.
CircRNA; positive feedback loop; colorectal cancer; PDIA4; SP1 | Introduction Colorectal cancer (CRC) is the third most prevalent cancer globally, accounting for approximately 10% of all cancer occurrences and ranking as the second leading cause of cancer-related fatalities worldwide1-3. CRC develops insidiously *These authors contributed equally to this work. Correspondence to: Peng Zhao and Xun Jin E-mail: [13752085215@163.com](13752085215@163.com) [and jinx2354@163.com](and jinx2354@163.com) ORCID ID: [https://orcid.org/0000-0002-1550-2199](https://orcid.org/0000-0002-1550-2199) Received March 27, 2024; accepted April 29, 2024; published online June 21, 2024. Available [at www.cancerbiomed.org](at www.cancerbiomed.org) ©2024 The Authors. Creative Commons Attribution-NonCommercial 4.0 International License and frequently transpires without overt symptoms in the early phases, resulting in delayed diagnoses and constrained treatment alternatives in advanced stages. The current primary interventions for CRC include surgery, neoadjuvant radiotherapy (administered to rectal cancer patients), and adjuvant chemotherapy (ad

FAQs

What is the main focus of the study?

The study investigates how circPDIA4 influences colorectal cancer progression through a PDIA4/miR-9-5p/SP1 positive feedback loop.

How was circPDIA4 expression and cancer cell behavior evaluated?

CircPDIA4 levels in CRC cell lines and tissues were examined, and knockdown experiments assessed effects on invasion, migration, and proliferation. CCK-8 and Transwell assays were used for growth and invasion/migration assessment.

What molecular interactions support the proposed mechanism?

The study confirms circPDIA4 binding with miR-9-5p, and miR-9-5p binding to SP1. Rescue experiments further indicate that the circPDIA4/miR-9-5p/SP1 axis accelerates CRC development.

Sep 21, 2026

Uploaded by Skyler