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miR-4293 upregulates lncRNA WFDC21P by suppressing mRNA-decapping enzyme 2 to promote lung carcinoma proliferation.
- Source :
-
Cell death & disease [Cell Death Dis] 2021 Jul 23; Vol. 12 (8), pp. 735. Date of Electronic Publication: 2021 Jul 23. - Publication Year :
- 2021
-
Abstract
- Non-coding RNAs (ncRNAs) involve in diverse biological processes by post-transcriptional regulation of gene expression. Emerging evidence shows that miRNA-4293 plays a significant role in the development of non-small cell lung cancer. However, the oncogenic functions of miR-4293 have not been studied. Our results demonstrated that miR-4293 expression is markedly enhanced in lung carcinoma tissue and cells. Moreover, miR-4293 promotes tumor cell proliferation and metastasis but suppresses apoptosis. Mechanistic investigations identified mRNA-decapping enzyme 2 (DCP2) as a target of miR-4293 and its expression is suppressed by miR-4293. DCP2 can directly or indirectly bind to WFDC21P and downregulates its expression. Consequently, miR-4293 can further promote WFDC21P expression by regulating DCP2. With a positive correlation to miR-4293 expression, WFDC21P also plays an oncogenic role in lung carcinoma. Furthermore, knockdown of WFDC21P results in functional attenuation of miR-4293 on tumor promotion. In vivo xenograft growth is also promoted by both miR-4293 and WFDC21P. Overall, our results establish oncogenic roles for both miR-4293 and WFDC21P and demonstrate that interactions between miRNAs and lncRNAs through DCP2 are important in the regulation of carcinoma pathogenesis. These results provided a valuable theoretical basis for the discovery of lung carcinoma therapeutic targets and diagnostic markers based on miR-4293 and WFDC21P.<br /> (© 2021. The Author(s).)
- Subjects :
- Adult
Aged
Animals
Apoptosis genetics
Base Sequence
Carcinogenesis genetics
Carcinogenesis pathology
Carcinoma, Non-Small-Cell Lung genetics
Carcinoma, Non-Small-Cell Lung pathology
Cell Line, Tumor
Cell Movement genetics
Cell Proliferation genetics
Female
Gene Knockdown Techniques
Humans
Male
Mice, Inbred BALB C
Mice, Nude
MicroRNAs genetics
Middle Aged
Models, Biological
Protein Binding
RNA, Long Noncoding metabolism
RNA, Messenger genetics
RNA, Messenger metabolism
STAT3 Transcription Factor metabolism
Mice
Gene Expression Regulation, Neoplastic
Lung Neoplasms genetics
Lung Neoplasms pathology
MicroRNAs metabolism
RNA, Long Noncoding genetics
Up-Regulation genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 12
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 34301920
- Full Text :
- https://doi.org/10.1038/s41419-021-04021-y