Mir-143 Slacks Off, Leaving DNMT3A To Run Wild In Colorectal Cancer

August 6, 2009 We like to think of epigenetics in terms of distinct areas like chromatin, DNA methylation and non-coding RNA (heck, we’ve even divided up the EpiGenie website that way), but more and more evidence is blurring the lines and showing us how these overlap. A recent publication from researchers at The Chinese University of Hong Kong gives us an example of how a non-coding RNA, miR-143, regulates DNA methylation by targeting DMNT3A in colorectal cancer (CRC).

While studying the role of miRNAs in CRC, the group in Hong Kong zeroed in on one in particular, miR-143, which has been previously reported to be down regulated in various cancers. To profile miRNA expression of colorectal cancer, Ng  and colleagues profiled 95 cancer related miRNAs arrayed in a plate format using the OncoMir platform (System Biosciences). After verifying miR-143 downregulation in pooled RNA samples from CRC tumor tissues and adjacent non-cancerous tissues, the researchers expanded their interrogation, looking at miR-143 expression in 30 patient samples and 7 human colon cancer cell lines with SBI’s QuantiMir small RNA qRT-PCR kit; thoroughly confirming miR-143 downregulation in CRC. So, is miR-143 a ringleader, or a follower in this mess?

To figure out if miR-143 was indeed a key player in CRC, the crew zeroed in on its potential targets by consulting the various target prediction oracles like PicTar, TargetScan and miRanda, which pinned DNMT3A as a target. After assaulting their model with a series of functional analysis experiments, they found:

• Ectopic expression of miR-143 led to downregulated DMNT3A and inhibited CRC cell growth

• Reporter assays showed that DNMT3A was a direct target of miR-143

• Knockdown of DNMT3A resulted in reduced CRC cell growth

• DNMT3A and miR-143 expression were inversely correlated in primary CRC tissues.

The team suggests a potential use for regulators like miR-143 that act as a natural DNMT inhibitor in therapies. Who knows, it might not be too long before we see ncRNAs like miR-143 thrown into therapeutic cocktails, so stay tuned, with all of the different tissues, non-coding RNAs and target genes out there, we’re sure to see more cases like this soon.

For a deeper dive into the details, check out British Journal of Cancer, August 2009

If you want the full scoop on the some of the snazzy tools used by this team, head over to System Bio’s site and read up on the OncoMir Collection, QuantiMir Kits and other miRNA related products.