Abstract
In humans, zinc finger protein 671 (ZNF671) is a type of transcription factor. However, the contribution of tumor heterogeneity to the functional role of ZNF671 remains unknown. The present study aimed to determine the functional states of ZNF671 in cancer single cells based on single-cell sequencing datasets (scRNA-seq). We collected cancer-related ZNF671 scRNA-seq datasets and analyzed ZNF671 in the datasets. We evaluated 14 functional states of ZNF671 in cancers and performed ZNF671 expression and function state correlation analysis. We further applied t-distributed stochastic neighbor embedding to describe the distribution of cancer cells and to explore the functional state of ZNF671 in cancer subgroups. We found that ZNF671 was downregulated in eight cancer-related ZNF671 scRNA-seq datasets. Functional analysis identified that ZNF671 might play a tumor suppressor role in cancer. The heterogeneous functional states of cell subgroups and correlation analysis showed that ZNF671 played tumor suppressor roles in heterogeneous cancer cell populations. Western blot and transwell assays identified that ZNF671 inhibited EMT, migration, and invasion of CNS cancers, lung cancer, melanoma, and breast carcinoma in vitro. These results from cancer single-cell sequencing indicated that ZNF671 played a tumor suppressor role in multiple tumors and may provide us with new insights into the role of ZNF671 for cancer treatment.
Highlights
Cancer is a complex ecosystem composed of cells with heterogeneous functional states, leading to both therapeutic resistance, and frequent cancer recurrence or metastasis, which poses a major obstacle to cancer diagnosis and treatment [1,2,3]
Our studies identified that zinc finger protein 671 (ZNF671) played a tumor suppressor role in breast invasive carcinoma (BRCA), cervical squamous cell carcinoma, and endocervical adenocarcinoma (CESC), head and neck squamous cell carcinoma (HNSC), kidney renal papillary cell carcinoma (KIRP), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD), and uterine corpus endometrial carcinoma (UCEC) [26, 27]
Krüppel-associated box (KRAB)-ZFPs are involved in regulating angiogenesis [36], apoptosis [37,38,39], the cell cycle [40, 41], inflammation [42], invasion and metastasis [43, 44], and stemness [45]
Summary
Cancer is a complex ecosystem composed of cells with heterogeneous functional states, leading to both therapeutic resistance, and frequent cancer recurrence or metastasis, which poses a major obstacle to cancer diagnosis and treatment [1,2,3]. Some tumor cells have high proliferative or apoptotic capacity, some have invasion and metastasis activities, some show stem-like properties, and some exhibit a quiescent state [4, 5]. These functionally heterogeneous cancer cells act cooperatively or competitively during tumor progression or metastasis, leading to distinct tumor phenotypes [6,7,8]. Single-cell mRNA-sequencing (scRNA-seq) provides a powerful tool for characterizing the omic-scale features of heterogeneous cell populations [9, 10]. The application of scRNA-seq in the clinic has the potential to change our approach to cancer management fundamentally [12]
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