Open Access

ARTICLE

ETV1 transcriptional manipulation of KIFC1 regulates the progression of pancreatic cancer

FANGFANG HU¹, ZHIBIN BAI², YANG WANG¹, HAODONG TANG³, JIAHUA ZHOU^1,*

1 Department of Hepatobiliary and Pancreatic Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China
2 Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China
3 Medical School, Southeast University, Nanjing, 210009, China

* Corresponding Author: JIAHUA ZHOU. Email:

(This article belongs to the Special Issue: Novel Biomarkers and Treatment Strategies in Solid Tumor Diagnosis, Progression, and Prognosis)

Oncology Research 2025, 33(7), 1723-1737. https://doi.org/10.32604/or.2025.059631

Received 13 October 2024; Accepted 06 March 2025; Issue published 26 June 2025

Abstract

Background: Kinesin-14 family protein 1 (KIFC1) is abnormally overexpressed in various cancers, and the transcription factor ETS variant 1 (ETV1) is an oncogenic transcription factor in tumors. The potential binding sites on the KIFC1 promoter by ETV1 were observed; however, no evidence supports that ETV1 targets KIFC1. Aims: This study aimed to investigate the relationship between KIFC1 and ETV1, and their effects and mechanisms in pancreatic cancer. Methods: Pan-cancer analysis of KIFC1 expression was performed in GEPIA2 database. KIFC1 expression levels were determined by immunohistochemistry (IHC) in our pancreatic cancer cohort. The correlation between KIFC1 expression and prognosis, tumor mutation burden, tumor purity, mismatch repair, and high-frequency tumor mutated genes was analyzed using a series of bioinformatic tools. ETV1 targeting of KIFC1 promoter transcription was determined using luciferase reporter assay. KIFC1 knockdown and ETV1 overexpression were used to determine the role of the ETV1/KIFC1 axis in cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells in vitro and tumor growth in vivo. Result: KIFC1 expression was increased in clinical specimens and pancreatic cancer cell lines and positively correlated with tumor mutation burden, tumor purity, mismatch repair, and KRAS and TP53 mutations. High KIFC1 expression was significantly associated with poor prognosis. Knockdown of KIFC1 suppressed the proliferation, migration, and invasion of pancreatic cancer cells and tumor growth. ETV1 overexpression increased KIFC1 expression and affected KIFC1 transcription. ETV1 overexpression reversed the role of KIFC1 knockdown in inhibiting cell proliferation, invasion, migration, and EMT, as validated in vivo. Conclusions: KIFC1 serves as a tumor activator in pancreatic cancer by promoting proliferation, migration, invasion, and tumor growth, which may be partly manipulated by ETV1.

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