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PubMed2025

Circular RNAs orchestrating breast cancer hallmarks: bridging tumor biology and therapy resistance.

Breast cancer (BC) remains a leading cause of cancer-related mortality among women worldwide, with treatment resistance posing a significant clinical challenge. Circular RNAs (circRNAs), a class of non-coding RNAs, have gained increasing attention as key regulators of gene expression, influencing BC pathogenesis, progression, and therapeutic response. This review explores the mechanistic insights into circRNA functions in BC, focusing on their involvement in tumor proliferation, metabolic reprogramming, epithelial-mesenchymal transition (EMT), angiogenesis, metastasis, and apoptosis. Additionally, we highlight the crosstalk between circRNAs and microRNAs, emphasizing their potential as diagnostic and prognostic biomarkers. Beyond their roles in tumor biology, circRNAs are implicated in drug resistance, modulating responses to chemotherapy, targeted therapy, and endocrine treatment. Despite their promising applications, challenges remain, including the complexity of circRNA interactions, and the development of robust preclinical models. Addressing these challenges through interdisciplinary research integrating genomics, transcriptomics, and functional studies will pave the way for circRNA-based therapeutic strategies and personalized medicine approaches in BC management.

Humans↗
PubMed1988

Transformation of Neurospora crassa with the trp-1 gene and the effect of host strain upon the fate of the transforming DNA.

Neurospora trp-1+ transformants, obtained by transforming a trp-1 inl strain with plasmid DNA containing the wild type trp1+ gene, were characterized by genetic and Southern blot analyses. The transforming trp-1 gene integrated at or near the resident site in all of the trp-1+ transformants obtained with circular DNA or DNA cut within the trp-1 coding region. The frequency of homologous integration decreased substantially when the donor DNA was cleaved outside the trp-1 coding region. The transformants were very stable mitotically and, in general, also showed meiotic stability. Analysis of trp-1+ transformants obtained with another recipient strain, trp-1+ ga-2 aro-9 inl, showed that homologous integration of donor DNA occurred in only 20% of the transformants, whether circular or linear DNA was used. Thus, the host strain employed for transformation appears to be a major factor in determining the fate of transforming DNA. Southern blot analysis of transformants showed that integration of the transforming DNA at the homologous site occurred by double crossover or gene conversion events rather than by insertion of the entire plasmid DNA. Multiple and apparently non functional integration events were observed in some transformants.

DNA Restriction Enzymes↗
PubMed1976

Isolation and characterization of the protein coded by gene A of bacteriophage phiX174 DNA.

Replication of phiX174 circular replicative form (RFI) DNA by extracts of Escherichia coli infected with bacteriophage phiX174 (amber in gene A) requires the phiX174 gene A product. This requirement has been used as an assay for the isolation of this protein. The gene A product (purified 4000-fold) caused relaxation of superhelical phiX174 RFI and formation of discontinuities in the viral strand of phiX174 RFI uniquely situated in the A region of the genome, and yielded a complex after interacting with phiX174 RFI that is active in replication of phiX RFI.

Coliphages↗
PubMed1974

The amplified ribosomal DNA of dytiscid beetles.

During oogenesis in many animals there is a massive extrachromosomal synthesis of the genes for ribosomal RNA. In Dytiscid beetles, as in the toad Xenopus, the amplified ribosomal DNA occurs as circular molecules of different sizes. The circles fall into size classes that are integral multiples of a unit circle. It is probable that the unit circle contains the coding sequence for one precursor ribosomal RNA molecule plus accompanying spacer sequences.

Animals↗
PubMed2026

Endosymbiotic theory of aging revisited: Age-related leakage of mitochondrial dsDNA/RNA stimulates cytosolic nucleic acid sensors which remodel the immune network and promote the aging process.

About 1.5-2 billion years ago, an endosymbiosis between aerobic α-proteobacteria and anaerobic archaeal cells generated mitochondria, i.e., organelles capable of producing oxidative energy. The bacterial genome was fundamentally reduced and a circular mitochondrial genome evolved containing mainly the genes coding for the subunits of the electron transport chain. Before the symbiotic event, there existed a virus-host co-evolution which involved the development of sensors for detecting dangerous viral DNA/RNA molecules. Endosymbiosis supplied eukaryotic cells not only with an oxidative powerhouse to allow the evolution of more complex multicellular organisms but it also meant that cells now housed an organelle which was able to generate reactive oxygen species (ROS) and to leak mitochondrial DNA (mtDNA) and double-stranded RNA (dsRNA) into the cytoplasm. There is now abundant evidence that during aging and age-related diseases mitochondria are prone to release both mtDNA and dsRNA. In the cytoplasm, mtDNA/dsRNA molecules activate a number of cytosolic nucleic acid sensors leading to the secretion of type-1 interferons (IFN) and many other cytokines which promote an age-related proinflammatory state. Currently, it is known that mtDNA can activate the cGAS-STING pathway, AIM2 inflammasomes, IFI16 receptors, and ZBP1 sensors and in addition mitochondrial dsRNA stimulates RIG-1/MDA5 signaling. Interestingly, there is abundant evidence that all these receptors are drivers of cellular senescence and inflammaging. For decades, there has been mounting evidence that mitochondria have a crucial role in the aging process. We will examine this question from the perspective of evolution and propose that mitochondrial evolution created an endogenic source for the leakage of dangerous mtDNA/dsRNA which subsequently stimulated cytosolic DNA/RNA sensors, an evolutionarily conserved viral defence mechanism. It seems that these two evolutionary events provided not only the basis for the inevitable process of aging but also ensuring the death of parental organisms.

Aging↗
PubMed1975

Insertion of a rabbit beta-globin gene sequence into an E. coli plasmid.

Double stranded DNA has been synthesized in vitro from rabbit globin messenger RNA and elongated with homopolymeric dG tails. An E. coli plasmid was cleaved by EcoRI. The cohesive ends were repaired and dC tails added, to permit reconstitution of the EcoRI sites upon annealing with the dG elongated globin DNA. Transformation of E. coli with the globin-plasmid DNA hybrid has yielded a clone which harbours a recombinant plasmid (pCR1-betaG1), as demonstrated by hybridization experiments with radioactive globin cDNA. The sequence carried by the recombinant plasmid corresponds to part of the gene sequence coding for the beta chain of rabbit globin. Circular DNA of the purified recombinant plasmid exhibits sensitivity to EcoRI.

Animals↗
PubMed2025

Quantitative Real-Time PCR for Circular RNA Detection and Analysis.

In eukaryotes, nearly 2% of the genome represented by the coding proteins. However, emerging evidence suggest more than 75% of the human genome referred to as noncoding part also plays a crucial role in governing major regulatory pathways. Noncoding RNAs can be categorized into several groups, such as microRNAs (miRNAs), small nuclear RNA (snRNAs), small nucleolar RNA (snoRNAs), transfer RNA (tRNA), and circular RNA (circRNAs), which contribute to this regulatory landscape. Circular RNAs (circRNAs) are identified as a new class of regulatory noncoding RNAs with gene regulatory roles by acting as miRNA or RNA binding protein sponges or interacting with proteins. Researchers employ quantitative real-time PCR methods to examine circular RNA expression utilizing divergent primers for identification and quantification.

RNA, Circular↗
PubMed1979

Nucleotide sequence analysis of viable deletion mutants lacking segments of the simian virus 40 genome coding for small t antigen.

The deletions in nine viable simian virus 40 mutants have been mapped by direct DNA sequence analysis. The mutant DNAs lack small segments of the early region of the viral chromosome (between 0.535 and 0.600 map unit). The deletions are all located in the region which is removed from the large T antigen transcript by splicing. No one deletion removes this entire region, but no part of this segment is conserved in all of the mutants except for several nucleotides near the splice points of the transcript. Although the deletions do not alter the region coding for the large T polypeptide, they do delete portions of the segment coding for the C-terminal half of the small t polypeptide.

Antigens, Viral↗
PubMed2025

Expression regulation network in papillae of sea cucumbers: Whole-transcriptome and DNA methylation datasets.

To elucidate the expression regulation network of papilla size of sea cucumbers (Apostichopus japonicus), the whole-transcriptome and DNA methylome datasets of different sizes of papillae in sea cucumbers were generated. Average clean bases of whole-transcriptome (16.35 G) and DNA methylome (28.92 G) were obtained using RNA sequencing and whole-genome bisulfite sequencing techniques. A total of 3,188 ceRNA networks were also identified including 3,081 long non-coding RNAs (lncRNA)/microRNAs (miRNA)/mRNA networks and 107 circular RNA (circRNA)/miRNA/mRNA networks. Methylome data indicate that there were 3,307 and 3,776 differentially methylated regions (DMRs) with high-level methylation as well as 3,125 and 3,016 DMRs with low-level methylation in big papillae compared to small papillae. The identified DMRs were mainly distributed in introns, promotors, or exons. The whole-transcriptome and DNA methylome datasets generated from this study not only established a robust theoretical foundation (especially from the epigenetic aspect) for elucidating expression regulation network determining papilla size in sea cucumbers but also can be a valuable resource of biomarker mining for papilla appearance-based selective breeding in sea cucumbers.

DNA Methylation↗
PubMed1987

Sequence of the cDNA encoding the laminin B1 chain reveals a multidomain protein containing cysteine-rich repeats.

Laminin is a basement membrane-specific glycoprotein (800 kDa) consisting of three chains: A, B1, and B2. Laminin has diverse biological functions, which include stimulating epithelial cell growth and differentiation. We have isolated two overlapping cDNA clones that span 5.9 kilobases and code for the entire B1 chain of mouse laminin. The nucleotide sequence of the clones reveals a 5358-base pair open reading frame that potentially codes for 1786 amino acids, including 20 amino acids of a presumptive signal peptide. Analysis of the deduced protein sequence predicts that the B1 chain has seven distinct domains that include cysteine-rich repeats, alpha-helical, and globular structures. Part of the cysteine-rich region is homologous to epidermal growth factor and other proteins that contain epidermal growth factor-like repeats.

Amino Acid Sequence↗
PubMed1979

Length heterogeneity of amplified circular rDNA molecules in oocytes of the house cricket Acheta domesticus (Orthoptera: Gryllidae).

Amplification of the genes coding for rRNA occurs in the oocytes of a wide variety of organisms. The amplification process appears to be mediated through a rolling-circle mechanism. The approximate molecular weight of the smallest rDNA circles is equivalent to the estimated combined molecular weight of DNA which codes for a single ribosomal RNA precursor molecule and an associated non-transcribed spacer DNA sequence. RNA-DNA hybridization studies carried out on oocytes of the house cricket, Acheta domesticus, suggest that DNA coding for rRNA accounts for only a small fraction of the rDNA satellite, all of which is amplified in the oocyte. In order to test the possibility that the remainder of the amplified rDNA represents spacer and to determine whether a rolling-circle mechanism might also be involved in amplification in A. domesticus oocytes, rDNA was isolated from ovaries of A. domesticus and spread for electron microscopy. A large proportion of the rDNA isolated from ovaries is circular, while main-band DNA and rDNA prepared from other tissues demonstrates few if any circles. The mean size of the smallest rDNA circles is approximately 8 times longer than the length estimated for DNA which codes for 18S and 28 S rRNA. Denaturation mapping shows the rDNA circles to contain two major readily denaturing regions located about equidistant from one another on the circle. Each readily denaturing region accounts for 4--6% of the total DNA in the circle. The fact that only 12% of the average molecule is required to code for A. domesticus 18S and 28S rRNA is consistent with the hybridization data. Considerable size heterogeneity exists in the length of the smallest class of rDNA molecules. In the rDNA of other species such heterogeneity has been shown to reside in the non-transcribed spacer.

Animals↗
PubMed1992

Immunoglobulin V gene replacement is caused by the intramolecular DNA deletion mechanism.

Circular DNA resulting from V gene replacement was studied with an A-MuLV transformed cell line containing ablts. This cell line undergoes V gene replacement at elevated temperatures in the immunoglobulin (Ig) heavy chain (H) gene. Examination of circular DNA revealed that a heptamer-related sequence (TACTGTG) within the coding region of VDJ was joined to the recombination signal sequence (RSS) of a germline VH segment. This provides direct evidence for a intramolecular DNA deletion mechanism for V gene replacement. In the pre-B cell line as well as in in vivo lymphocytes, unusual circular DNAs were found which were structurally similar to the V gene replacement circles. They represented excision products of the deletion type recombination between one complete RSS and a heptamer-like sequence in the Ig H region.

Animals↗
PubMed1987

Partial characterization of a low molecular weight human collagen that undergoes alternative splicing.

A cDNA library prepared from RNA isolated from a cultured human tumor cell line, HT-1080, was screened with a mouse cDNA clone coding for part of the -Gly-Xaa-Yaa- domain of the alpha 2(IV) collagen chain. Four overlapping cDNA clones were characterized that coded for a low molecular weight human collagen. The cDNA clones did not, however, code for the short-chain collagens, types IX and X. The amino acid sequences derived from the clones resembled type IV collagen in that there were short interruptions in the repeating -Gly-Xaa-Yaa- sequence. The noncollagenous, carboxyl-terminal domain was, however, much shorter and contained only 18 amino acid residues. Interestingly, one of the cDNA clones contained an additional 36 nucleotides not found in an overlapping clone. The 36 nucleotides encoded four -Gly-Xaa-Yaa- repeats without changing the reading frame. Nuclease S1 mapping demonstrated that the difference between the clones was due to existence of two different mRNAs. A synthetic 24-residue peptide corresponding to the last two -Gly-Xaa-Yaa- triplets and the entire carboxyl-terminal domain was used to generate polyclonal antibodies. Electrophoretic transfer blot analysis of HT-1080 cells and normal human skin fibroblasts identified two polypeptides, Mr 67,000 and Mr 62,000, that were sensitive to bacterial collagenase.

Amino Acid Sequence↗