Application of PCR-based approaches for evaluation of cell-free DNA fragmentation in colorectal cancer.

Cell-free DNA (cfDNA) testing is the core of most liquid biopsy assays. In particular, cfDNA fragmentation features could facilitate non-invasive cancer detection due to their interconnection with tumor-specific epigenetic alterations. However, the final cfDNA fragmentation profile in a purified sample is the result of a complex interplay between informative biological and artificial technical factors.

The Detection of Cancer Epigenetic Traces in Cell-Free DNA.

Nucleic acid fragments found in blood circulation originate mostly from dying cells and carry signs pointing to specific features of the parental cell types. Deciphering these clues may be transformative for numerous research and clinical applications but strongly depends on the development and implementation of robust analytical methods. Remarkable progress has been achieved in the reliable detection of sequence alterations in cell-free DNA while decoding epigenetic information from methylation and fragmentation patterns requires more sophisticated approaches.

Breast cancer organoid model allowed to reveal potentially beneficial combinations of 3,3'-diindolylmethane and chemotherapy drugs.

Epigenetic alterations represent promising therapeutic targets in cancer treatment. Recently it was revealed that small molecules have the potential to act as microRNA silencers. Capacity to bind the discrete stem-looped structure of pre-miR-21 and prevent its maturation opens opportunities to utilize such compounds for the prevention of initiation, progression, and chemoresistance of cancer.

TATA-Like Boxes in RNA Polymerase III Promoters: Requirements for Nucleotide Sequences.

tRNA and some other non-coding RNA genes are transcribed by RNA polymerase III (pol III), due to the presence of intragenic promoter, consisting of boxes A and B spaced by 30-40 bp. Such pol III promoters, called type 2, are also intrinsic to Short Interspersed Elements (SINEs). The contribution of 5'-flanking sequences to the transcription efficiency of genes containing type 2 promoters is still studied insufficiently.

A 5'-3' terminal stem in small non-coding RNAs extends their lifetime.

4.5SI and 4.5SH are two non-coding RNAs about 100nt long, synthesized by RNA polymerase III in cells of various rodents including mice, rats, and hamsters.

Complementarity of end regions increases the lifetime of small RNAs in mammalian cells.

Two RNAs (4.5SH and 4.5SI) with unknown functions share a number of features: short length (about 100 nt), transcription by RNA polymerase III, predominately nuclear localization, the presence in various tissues, and relatively narrow taxonomic distribution (4 and 3 rodent families, respectively).

Additional box B of RNA polymerase III promoter in SINE B1 can be functional.

Many genes of small RNAs and short interspersed elements (SINEs) are transcribed by RNA polymerase III due to an internal promoter that is composed of two boxes (A and B) spaced by 30-45bp. Rodent SINE B1 originated from 7SL RNA, and a 29-bp tandem duplication took place in B1 at an early stage of its evolution. As a result of this duplication, an additional box B (named B') located at a distance of 79-82bp from box A arose in SINE B1.

5'-flanking sequences can dramatically influence 4.5SH RNA gene transcription by RNA-polymerase III.

4.5SH RNA is a 94 nt small nuclear RNA with an unknown function. Hundreds of its genes are present in the genomes of rodents of six families including Muridae.

Evolutionary history of 4.5SH RNA.

4.5SH RNA is a 94-nt small RNA with unknown function. This RNA is known to be present in the mouse, rat, and hamster cells; however, it is not found in human, rabbit, and chicken.