ZNF204P is a stemness-associated oncogenic long non-coding RNA in hepatocellular carcinoma
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Hepatocellular carcinoma is a major health burden, and thoughvarious treatments through much research are available, difficultiesin early diagnosis and drug resistance to chemotherapy-basedtreatments render several ineffective. Cancer stem cell model hasbeen used to explain formation of heterogeneous cell populationwithin tumor mass, which is one of the underlying causesof high recurrence rate and acquired chemoresistance, highlightingthe importance of CSC identification and understandingthe molecular mechanisms of CSC drivers. Extracellular CSCmarkerssuch as CD133, CD90 and EpCAM have been usedsuccessfully in CSC isolation, but studies have indicated thatincreasingly complex combinations are required for accurateidentification. Pseudogene-derived long non-coding RNAs areuseful candidates as intracellular CSC markers - factors that regulatepluripotency and self-renewal – given their cancer-specificexpression and versatile regulation across several levels. Here,we present the use of microarray data to identify stemness-associatedfactors in liver cancer, and selection of sole pseudogenederivedlncRNA ZNF204P for experimental validation. ZNF204Pknockdown impairs cell proliferation and migration/invasion. As the cytosolic ZNF204P shares miRNA binding sites with OCT4and SOX2, well-known drivers of pluripotency and self-renewal,we propose that ZNF204P promotes tumorigenesis through themiRNA-145-5p/OCT4, SOX2 axis.
Abstract
Hepatocellular carcinoma is a major health burden, and thoughvarious treatments through much research are available, difficultiesin early diagnosis and drug resistance to chemotherapy-basedtreatments render several ineffective. Cancer stem cell model hasbeen used to explain formation of heterogeneous cell populationwithin tumor mass, which is one of the underlying causesof high recurrence rate and acquired chemoresistance, highlightingthe importance of CSC identification and understandingthe molecular mechanisms of CSC drivers. Extracellular CSCmarkerssuch as CD133, CD90 and EpCAM have been usedsuccessfully in CSC isolation, but studies have indicated thatincreasingly complex combinations are required for accurateidentification. Pseudogene-derived long non-coding RNAs areuseful candidates as intracellular CSC markers - factors that regulatepluripotency and self-renewal – given their cancer-specificexpression and versatile regulation across several levels. Here,we present the use of microarray data to identify stemness-associatedfactors in liver cancer, and selection of sole pseudogenederivedlncRNA ZNF204P for experimental validation. ZNF204Pknockdown impairs cell proliferation and migration/invasion. As the cytosolic ZNF204P shares miRNA binding sites with OCT4and SOX2, well-known drivers of pluripotency and self-renewal,we propose that ZNF204P promotes tumorigenesis through themiRNA-145-5p/OCT4, SOX2 axis.
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