NDLI: Experimental verification of a predicted novel microRNA located in human PIK3CA gene with a potential oncogenic function in colorectal cancer

Content Provider	Springer Nature Link
Author	Saleh, Ali Jason Soltani, Bahram M. Dokanehiifard, Sadat Medlej, Abdallah Tavalaei, Mahmoud Mowla, Seyed Javad
Copyright Year	2016
Abstract	PI3K/AKT signaling is involved in cell survival, proliferation, and migration. In this pathway, PI3Kα enzyme is composed of a regulatory protein encoded by p85 gene and a catalytic protein encoded by PIK3CA gene. Human PIK3CA locus is amplified in several cancers including lung and colorectal cancer (CRC). Therefore, microRNAs (miRNAs) that are encoded within the PIK3CA gene might have a role in cancer development. Here, we report a novel microRNA named PIK3CA-miR1 (EBI accession no. LN626315), which is located within PIK3CA gene. A DNA segment corresponding to PIK3CA-premir1 sequence was transfected in human cell lines that resulted in generation of mature exogenous PIK3CA-miR1. Following the overexpression of PIK3CA-miR1, its predicted target genes (APPL1 and TrkC) were significantly downregulated in the CRC-originated HCT116 and SW480 cell lines, detected by qRT-PCR. Then, dual luciferase assay supported the interaction of PIK3CA-miR1 with APPL1 and TrkC transcripts. Endogenous PIK3CA-miR1 expression was also detected in several cell lines (highly in HCT116 and SW480) and highly in CRC specimens. Consistently, overexpression of PIK3CA-premir1 in HCT116 and SW480 cells resulted in significant reduction of the sub-G1 cell distribution and apoptotic cell rate, as detected by flowcytometry, and resulted in increased cell proliferation, as detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. PIK3CA-miR1 overexpression also resulted in Wnt signaling upregulation detected by Top/Fop assay. Overall, accumulative evidences indicated the presence of a bona fide novel onco-miRNA encoded within the PIK3CA oncogene, which is highly expressed in colorectal cancer and has a survival effect in CRC-originated cells.
Starting Page	14089
Ending Page	14101
Page Count	13
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	37
Issue Number	10
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-08-10
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	PI3K signaling PIK3CA-miR1 Colorectal cancer Oncogene APPL1 TrkC Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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