Long noncoding RNA SOX2OT maintains the stemness of pancreatic cancer cells by regulating DEK via interacting with miR-200a/141.

Abstract

OBJECTIVE:

Long noncoding RNA sex determination region of Y chromosome (SRY)-related HMG-box (SOX) is involved in the development of various cancers. However, the molecular mechanism of SOXOT, an overlapping transcript of SOX, in pancreatic cancer (PC) is still undefined. We aimed to explore the epigenetic function of SOX2OT and its downstream factors in advanced PC.

PATIENTS AND METHODS:

The levels of SOX2OT, miRNA, and DEK proto-oncogene (DEK) in pancreatic cancer tissues and cell lines were evaluated by quantitative polymerase chain reaction (qPCR). The log-rank test was applied to evaluate the role of high SOX2OT levels in shortening the overall survival of pancreatic cancer patients. The Chi-squared test was made to assess the relation between SOX2OT expression and clinicopathological features of PC patients. Colony assay tested the cell proliferation of PC cells with SOX2OT knockdown. Flow cytometry and Western blotting were used to determine the stemness of tumor cells in vitro. The underlying regulatory mechanism between SOX2OT and miR-200a/141 was predicted by bioinformatics and verified by RNA transfection, qPCR, and Western blotting. Mice xenograft models were applied to determine the promoting effects of SOX2OT on PC in vivo.

RESULTS:

The expression of SOX2OT in PC tissues and cell lines is strongly elevated. High levels of SOX2OT expression are more likely to present in patients with advanced TNM stage, positive CD44, and poor overall survival. SOX2OT overexpression promotes proliferation and stemness maintaining of PC cells in vitro and boosts tumor growth in vivo. Furthermore, SOX2OT upregulates DEK expression by binding to miR-200a/141 as a competing endogenous RNA.

CONCLUSIONS:

DEK induced by SOXOT- miR-200a/141 axis may markedly promote stem cell property of PC, resulting in an advanced stage and inferior survival. These findings suggest the SOX2OT-DEK axis as a novel therapeutic target in PC.

• Authors: C-S Liu, Q Zhou, Y-D Zhang, Y Fu
• Journal: European review for medical and pharmacological sciences (Eur Rev Med Pharmacol Sci) Vol. 24 Issue 5 Pg. 2368-2379 (03 2020) ISSN: 2284-0729 [Electronic] Italy
• PMID: 32196588 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)

Chemical References

• Chromosomal Proteins, Non-Histone
• DEK protein, human
• MAS1 protein, human
• MIRN141 microRNA, human
• MIRN200 microRNA, human
• MicroRNAs
• Oncogene Proteins
• Poly-ADP-Ribose Binding Proteins
• Proto-Oncogene Mas
• RNA, Long Noncoding
• long non-coding RNA Sox2ot, human

Topics

• Animals
• Cells, Cultured
• Chromosomal Proteins, Non-Histone (genetics, metabolism)
• Female
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Oncogene Proteins (genetics, metabolism)
• Pancreatic Neoplasms (metabolism, pathology)
• Poly-ADP-Ribose Binding Proteins (genetics, metabolism)
• Proto-Oncogene Mas
• RNA, Long Noncoding (genetics, metabolism)