LncRNA OIP5-AS1 is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors

被引：53

作者：

Arunkumar, Ganesan ^{[1
]}

Anand, Shankar ^{[1
]}

Raksha, Partha ^{[1
]}

Dhamodharan, Shankar ^{[1
]}

Rao, Harikrishnan Prasanna Srinivasa ^{[2
,3
]}

Subbiah, Shanmugam ^{[2
,3
]}

Murugan, Avaniyapuram Kannan ^{[4
]}

Munirajan, Arasambattu Kannan ^{[1
]}

机构：

[1] Univ Madras, Dr ALM PG Inst Basic Med Sci, Dept Genet, Taramani Campus, Madras 600113, Tamil Nadu, India

[2] Royapettah Govt Hosp, Ctr Oncol, Madras 600014, Tamil Nadu, India

[3] Kilpauk Med Coll, Madras 600014, Tamil Nadu, India

[4] King Faisal Specialist Hosp & Res Ctr, Dept Mol Oncol, Riyadh 11211, Saudi Arabia

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

关键词：

LONG NONCODING RNA; COLORECTAL-CANCER; NECK-CANCER; CELLS; CELF1; EXPRESSION; MICRORNA; HEAD; PROLIFERATION; DYSREGULATION;

D O I：

10.1038/s41598-018-25451-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Long non-coding RNAs (lncRNAs) play an important role in the regulation of key cellular processes in early development and cancer. LncRNA Oip5-as1 facilitates stem cell self-renewal in mouse by sponging mmu-miR-7 and modulating NANOG level, yet its role in cancer is less understood. We analyzed OIP5-AS1 expression in oral tumors and in TCGA datasets. We observed overexpression of OIP5-AS1 in oral tumors (P < 0.001) and in tumors of epithelial origin from TCGA. OIP5-AS1 expression was strongly associated with undifferentiated tumors (P = 0.0038). In silico analysis showed miR-7 binding site is conserved in mouse and human OIP5-AS1. However, human NANOG 3'-UTR lost the binding site for hsa-miR-7a-3. Therefore, we screened for other miRNAs that can be sponged by OIP5-AS1 and identified six potential miRNAs and their downstream target genes. Expression analysis showed downregulation of miRNAs and upregulation of downstream target genes, particularly in undifferentiated tumors with high-level of OIP5-AS1 suggesting OIP5-AS1 could post-transcriptionally modulate the downstream target genes. Further, systematic epigenomic analysis of OIP5-AS1 promoter revealed binding motifs for MYC, NANOG and KLF4 suggesting that OIP5-AS1 could be transactivated by stemness-associated transcription factors in cancer. OIP5-AS1 overexpression in undifferentiated oral tumors may be suggestive of enhanced cancer stemness, and consequently, poor clinical outcome.

引用

页数：13

共 53 条

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