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. 2025 Feb 28;33(3):591-604.
doi: 10.32604/or.2024.050548. eCollection 2025.

The regulatory role of ZFAS1/ miRNAs/mRNAs axis in cancer: a systematic review

Rahul Kumar Singh  1 , Surojit Mandal  1 , Adrija Mohanta  1 , Ritu Yadav  1 , Rajiv Ranjan Kumar  1 , Rinku Khatkar  1 , Vivek Uttam  1 , Uttam Sharma  1 , Manjit Kaur Rana  2 , Manju Jain  3 , Hardeep Singh Tuli  4 , Aklank Jain  1
Affiliations

The regulatory role of ZFAS1/ miRNAs/mRNAs axis in cancer: a systematic review

Rahul Kumar Singh et al. Oncol Res. .

Abstract

Objectives: Recently, we and others have demonstrated the involvement of Zinc Finger Antisense 1 (ZFAS1) in cancer development. However, the intricate interplay of ZFAS1 with miRNAs and mRNAs remains to be fully understood.

Materials and methods: We followed PRISMA guidelines to retrieve and assess the available literature on the topic "ZFAS1/miRNA/mRNA axis" and "Cancer" from databases such as PubMed, Google Scholar, and ScienceDirect. We also used bioinformatic webtools for analyzing the potential miRNA targets of ZFAS1 and its role in survival of cancer patients along with their role in various biological functions and pathways.

Results: Our literature search and bioinformatic analysis reveals that ZFAS1 serves as a sponge for numerous miRNAs. Among the various targeted miRNAs, miR-150-5p stands out as significantly correlated with ZFAS1 across multiple databases (p-value = 3.27e-16, R-value = -0.346). Additionally, our Kaplan-Meier survival analysis indicates a noteworthy association between ZFAS1 expression levels and overall poor prognosis and survival rates in ovarian, sarcoma, and pancreatic cancers. We also underscore the involvement of various signaling pathways, including Signal Transducer and Activator of Transcription 3 (STAT3), Spindle and Kinetochore-associated Protein 1 (SKA1), Lysophosphatidic acid receptor 1 (LPAR1), and Wnt β-catenin, in cancer development through the ZFAS1/miRNAs/mRNAs axis. Furthermore, we identify ZFAS1's pivotal roles in diverse molecular processes, such as RNA binding and ribonucleoprotein formation.

Conclusion: In conclusion, this review comprehensively summarizes the latest advancements in understanding the regulatory relationships among ZFAS1, miRNAs, and mRNAs, emphasizing their collective role in cancer development to propose innovative avenues for cancer treatment. We believe that the intricate relationship among the ZFAS1-miRNA-mRNA axis may yield potential therapeutic targets for effective cancer management.

Keywords: Cancer biomarker; LncRNA; Zinc finger antisense 1 (ZFAS1); mRNAs; miRNA.

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Conflict of interest statement

The authors declare no conflicts of interest to report regarding the present study.

Figures

Figure 1
Figure 1. Heatmap showing approximate Log2 Fold change in lncRNA ZFAS1 expression level associated with different cancer types (graph prepared using GraphPad v8.0).
Figure 2
Figure 2. The PRISMA flow diagram depicting the process of literature search and study selection done using PubMed, Google Scholar and ScienceDirect related to ZFAS1/miRNA/mRNA axis and hallmarks of cancer. A total of 30 relevant articles are included in this review.
Figure 3
Figure 3. Schematic diagram showing different molecules and pathways associated with ZFAS1 and hallmarks of cancer. The upregulated and downregulated molecules/pathways are shown by up and down arrows, respectively.
Figure 4
Figure 4. ZFAS1 regulates cancer cell proliferation, metastasis, and invasion through sponging miRNAs. ZFAS1 sponges miR-100-3p, miR-150-5p, miR-590-3p, miR-497-5p, miR-892b and miR-124 (Figure made in BioRender.com, accessed 10 March 2024).
Figure 5
Figure 5. In-silico target prediction of lncRNA ZFAS1 using online databases starBase v2.0, RNAInter v4.0 and RAID v2.0. (A) GO Biological processes (B) GO Molecular processes (C) GO Cellular compartment (D) Venn diagram for miRNA targets of ZFAS1 made using Venny 2.0.
Figure 6
Figure 6. Plots of Kaplan-Meier estimate overall survival of a group of patients retrieved from TCGA database (https://ualcan.path.uab.edu/, accessed on 10 March 2024). (A) Breast cancer (BC) (B) Cholangiocarcinoma (CCA) (C) Colorectal cancer (CRC) (D) Esophageal squamous cell carcinoma (ESCC) (E) Bladder cancer (BLCA) (F) Ovarian cancer (OC) (G) Pancreatic cancer (PC) (H) Sarcoma (SARC).
Figure 7
Figure 7. Pearson correlation coefficient of ZFAS1 and miRNA obtained using starBase v2.0. (A) hsa-miR-497-5p (B) hsa-miR-150-5p (C) hsa-miR-124-3p (D) hsa-miR-589-5p (E) hsa-miR-7-5p (F) hsa-miR-193a-3p (G) hsa-miR-200b-3p (H) hsa-miR-190a-3p.
See this image and copyright information in PMC

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