PARP in colorectal cancer: Molecular mechanisms, immunity, clinical trials, and drug combinations.

The changes in cell homeostasis in the tumor microenvironment may affect the development of colorectal cancer (CRC). Genomic instability is an important factor. Persistent genomic instability leads to epigenetic changes, and mutations are a major factor in the progression of CRC. Based on these mechanisms, it is reasonable to link poly (ADP-ribose) polymerase (PARP) with the treatment of CRC. PARP is mainly involved in DNA repair, which has an essential role in the DNA damage response and prevention of DNA damage, and maintains oxidation and superoxide redox homeostasis in the intracellular environment of the tumor. This article reviews the latest research progress on PARP and PARP inhibitors (PARPi) in CRC. It mainly includes molecular mechanisms, immunity, clinical trials, and combination strategies of CRC. The research of PARPi in CRC has broad prospects, and the combinations with other drugs are the main research direction in the future.

Biological Functions of the DNA Glycosylase NEIL3 and Its Role in Disease Progression Including Cancer.

The accumulation of oxidative DNA base damage can severely disrupt the integrity of the genome and is strongly associated with the development of cancer. DNA glycosylase is the critical enzyme that initiates the base excision repair (BER) pathway, recognizing and excising damaged bases. The Nei endonuclease VIII-like 3 (NEIL3) is an emerging DNA glycosylase essential in maintaining genome stability. With an in-depth study of the structure and function of NEIL3, we found that it has properties related to the process of base damage repair. For example, it not only prefers the base damage of single-stranded DNA (ssDNA), G-quadruplex and DNA interstrand crosslinks (ICLs), but also participates in the maintenance of replication fork stability and telomere integrity. In addition, NEIL3 is strongly associated with the progression of cancers and cardiovascular and neurological diseases, is incredibly significantly overexpressed in cancers, and may become an independent prognostic marker for cancer patients. Interestingly, circNEIL3, a circular RNA of exon-encoded origin by NEIL3, also promotes the development of multiple cancers. In this review, we have summarized the structure and the characteristics of NEIL3 to repair base damage. We have focused on NEIL3 and circNEIL3 in cancer development, progression and prognosis.

Osteopontin and its downstream carcinogenic molecules: regulatory mechanisms and prognostic value in cancer progression.

Osteopontin (OPN) is a multifunctional phosphorylated glycoprotein that is expressed at significantly elevated levels in various cancers. OPN overexpression is closely associated with the development of cancer progression such as proliferation, metastasis, angiogenesis, apoptosis resistance, drug resistance, and immunosuppression, and may also be an independent prognostic biomarker for a variety of cancers. This review broadly summarizes the mechanisms that regulate the expression of downstream oncogenic molecules after OPN binds to integrin receptors or CD44 receptors, which involve a complex intracellular "signaling traffic network" (including key kinases, signaling pathways, and transcription factors). In addition, we review the prognostic value of OPN, OPN synergistic downstream oncogenic molecules in the female breast, non-small cell lung, prostate, colorectal, gastric, and hepatocellular carcinomas. The prognostic value of OPN in tissues or blood may vary due to differences in study subjects or detection methods, and this aspect of the study requires further systematization with a view to applying the detection of OPN to clinical applications. Importantly, based on the fact that the oncogenic effect of OPN correlates with the expression of the above-mentioned oncogenic molecules, this work may provide some help in the study of combination therapy targeting OPN and the above-mentioned oncogenic molecules.

Inhibition of adhesion of hepatocellular carcinoma cells to basement membrane components by receptor competition with RGD- or YIGSR-containing synthetic peptides.

A micropipette technique was used to investigate the effects of four synthetic peptides, YIGSR, CDPGYIGSR, RGDS and GRGDTP, on the adhesion of hepatocellular carcinoma (HCC) cells onto type IV collagen/laminin/fibronectin coated surfaces. Adhesion of HCC cells to laminin was found to be YIGSR- or CDPGYIGSR-dependent while that to fibronectin and type IV collagen was RGDS- or GRGDTP-dependent. The reduction in adhesion strengths of HCC cells was slight to moderate (up to 55%), and was dependent on the peptide concentration. The decrease in adhesion strengths was reversed by an increase in ligand coating concentration and was compromised by prolonged interaction of the cells with the surfaces. These results suggested that the inhibition was due to competitive retardation rather than to a blockade of adhesion strengthening. A simple asymptotic function was adopted to fit the correlation between the mean of cell adhesion strengths and peptide concentration within defined concentration ranges. Regression analysis showed that cell adhesion strengths appeared to approach a plateau with increasing concentration of the inhibitory peptides, which was not always uniform over the entire concentration range tested. Further reduction in adhesion strengths was observed at higher peptide concentrations. It is suggested that the constants obtained by fitting over a low peptide concentration range might be kinetically representative of the inhibition during early events of adhesion or attachment.