The role of CSTF2 in cancer: from technology to clinical application

ABSTRACT

A protein called cleavage-stimulating factor subunit 2 (CSTF2, additionally called CSTF-64) binds RNA and is needed for the cleavage and polyadenylation of mRNA. CSTF2 is an important component subunit of the cleavage stimulating factor (CSTF), which is located on the X chromosome and encodes 557 amino acids. There is compelling evidence linking elevated CSTF2 expression to the pathological advancement of cancer and on its impact on the clinical aspects of the disease. The progression of cancers, including hepatocellular carcinoma, melanoma, prostate cancer, breast cancer, and pancreatic cancer, is correlated with the upregulation of CSTF2 expression. This review provides a fresh perspective on the investigation of the associations between CSTF2 and various malignancies and highlights current studies on the regulation of CSTF2. In particular, the mechanism of action and potential clinical applications of CSTF2 in cancer suggest that CSTF2 can serve as a new biomarker and individualized treatment target for a variety of cancer types.

KEYWORDS:

• Cancer
• CSTF2
• RNA-binding protein
• prognosis

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

JD and YS conceived the presented study and drafted the manuscript. YL designed the figures and tables. YX reviewed the manuscript. DY modified the figures and tables. XW revised the grammar. HS, HZ and HL conceived the presented study and reviewed the draft. JD submitted the document for publication. All authors agreed on the final version.

Abbreviation

CSTF2/CSTF-64: cleavage stimulation factor subunit 2; CSTF: cleavage stimulating factor; HLA: human leucocyte antigen; 3’UTR: 3’untranslated region; NSCLC: non-small cell lung cancer; ATP: adenosine triphosphate; UCB: urothelial carcinoma of the bladder; BID: a pro-apoptotic member of the B-cell lymphoma-2 family; ZFP36L2: zinc finger protein 36, C3H type-like 2; HCC: hepatocellular carcinoma; TNBC: triple-negative breast cancer; PDAC: pancreatic ductal adenocarcinoma; ESCC: esophageal squamous cell carcinoma; TIMER: Tumor Immune Estimation Resource; APA: alternative polyadenylation; RAC1: Rac family small GTPase 1; ER: estrogen receptor; PR: progesterone receptor; EGF: epidermal growth factor; EGFR: epidermal growth factor receptors; ICB: immune checkpoint blockade; PI3K/AKT/mTOR: phosphatidylinositol 3’-kinase/protein kinase B/mammalian target of rapamycin; CPSF3: cleavage and polyadenylation specificity factor subunit 3; HLF: human lymphatic filariasis; RRM: RNA recognition motif; RBP: RNA binding proteins;

Additional information

Funding

This study was supported by the 512 Talent Cultivation Program of Bengbu Medical College [by51201313], Young Scientist Fund of Bengbu Medical College [2021byyfyyq02] Anhui Provincial Natural Science Foundation [KJ2021A0815], Anhui Medical University Clinical Foundation (2020xkj208), Anhui Biochemical Engineering Centre Research Platform Project [2023SYKFZ06].