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ZNF204P is a stemness-associated oncogenic long non-coding RNA in hepatocellular carcinoma
Ji-Hyun Hwang1, Jungwoo Lee1, Won-Young Choi1
1Interdisciplinary Program of Integrated OMICS for Biomedical Science, The Graduate School, Yonsei University, Seoul 03722, Korea.
Abstract:
Hepatocellular carcinoma is a major health burden, and though various treatments through much research are available, difficulties in early diagnosis and drug resistance to chemotherapy-based treatments render several ineffective. Cancer stem cell model has been used to explain formation of heterogeneous cell population within tumor mass, which is one of the underlying causes of high recurrence rate and acquired chemoresistance, highlighting the importance of CSC identification and understanding the molecular mechanisms of CSC drivers. Extracellular CSCmarkers such as CD133, CD90 and EpCAM have been used successfully in CSC isolation, but studies have indicated that increasingly complex combinations are required for accurate identification. Pseudogene-derived long non-coding RNAs are useful candidates as intracellular CSC markers - factors that regulate pluripotency and self-renewal - given their cancer-specific expression and versatile regulation across several levels. Here, we present the use of microarray data to identify stemness-associated factors in liver cancer, and selection of sole pseudogenederived lncRNA ZNF204P for experimental validation. ZNF204P knockdown impairs cell proliferation and migration/invasion. As the cytosolic ZNF204P shares miRNA binding sites with OCT4 and SOX2, well-known drivers of pluripotency and self-renewal, we propose that ZNF204P promotes tumorigenesis through the miRNA-145-5p/OCT4, SOX2 axis. [BMB Reports 2022; 55(6): 281-286].
Insights
This study identifies ZNF204P as a novel intracellular marker for liver cancer stem cells. Its knockdown inhibits tumor growth, suggesting a new therapeutic target for hepatocellular carcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Hepatocellular carcinoma (HCC) presents a significant global health challenge, often diagnosed late and exhibiting resistance to chemotherapy.
- The cancer stem cell (CSC) model explains tumor heterogeneity, recurrence, and chemoresistance, emphasizing the need for CSC identification and understanding their drivers.
- Current extracellular CSC markers (e.g., CD133, CD90, EpCAM) require complex combinations for accurate identification.
Discussion:
- Pseudogene-derived long non-coding RNAs (lncRNAs) are proposed as intracellular CSC markers due to their cancer-specific expression and regulatory roles in pluripotency and self-renewal.
- Microarray data analysis identified ZNF204P, a pseudogene-derived lncRNA, as a stemness-associated factor in liver cancer.
- Experimental validation showed that ZNF204P knockdown significantly impairs HCC cell proliferation, migration, and invasion.
Key Insights:
- ZNF204P functions as an intracellular marker for liver cancer stem cells.
- ZNF204P knockdown demonstrates potent anti-tumor effects on HCC cells.
- The lncRNA ZNF204P is proposed to promote tumorigenesis via the miRNA-145-5p/OCT4, SOX2 axis.
Outlook:
- ZNF204P represents a promising therapeutic target for overcoming chemoresistance and reducing recurrence in HCC.
- Further research into the regulatory network of ZNF204P could reveal additional therapeutic strategies for liver cancer.
- Understanding the role of pseudogene-derived lncRNAs in cancer stemness may lead to novel diagnostic and therapeutic approaches.
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