miR-373-3p promotes aerobic glycolysis in colon cancer cells by targeting MFN2.

MicroRNAs (miRNAs) are implicated in the development of cancers and may serve as potential targets for therapy. However, the functions and underlying mechanisms of miRNAs in cancers are not well understood. This work aims to study the role of miR-373-3p in colon cancer cells.

Circular RNA circHIPK2 inhibits colon cancer cells through miR-373-3p/RGMA axis.

Circular RNAs (circRNAs) have been implicated in cancer development. However, their regulation, function, and underlying mechanisms of action remain unclear. We found that circHIPK2 was downregulated in colon cancer, and low expression levels of circHIPK2 were associated with high tumor grade and poor patient survival.

Circular RNAs in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a term encompassing a few chronic inflammatory disorders that leads to damage of the intestinal tract. Although much progress has been made in understanding the pathology of IBD, the precise pathogenesis is not completely understood. Circular RNAs (circRNAs) are single-stranded, covalently closed, endogenous molecules in eukaryotes with a variety of biological functions.

PHD3 inhibits colon cancer cell metastasis through the occludin-p38 pathway.

Prolyl hydroxylase 3 (PHD3) hydroxylates HIFα in the presence of oxygen, leading to HIFα degradation. PHD3 inhibits tumorigenesis. However, the underlying mechanism is not well understood.

Hypoxia inducible factor prolyl hydroxylases in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic disease that is characterized by intestinal inflammation. Epithelial damage and loss of intestinal barrier function are believed to be the hallmark pathologies of the disease. In IBD, the resident and infiltrating immune cells consume much oxygen, rendering the inflamed intestinal mucosa hypoxic.

XBP1s acts as a transcription factor of IRE1α and promotes proliferation of colon cancer cells.

Upon ER stress, IRE1α is activated to splice XBP1 mRNA to generate XBP1s, a transcription factor that induces the expression of genes to cope with the stress. Expression of IRE1α is elevated in cancers and the IRE1α-XBP1s axis plays an important role in proliferation of cancer cells. However, the underlying mechanism is not well known.

PHD3 inhibits cell proliferation through hydroxylation of PAX2 at proline 9.

The oncoprotein transcription factor paired box 2 (PAX2) is aberrantly expressed in cancers, but the underlying mechanism remains elusive. Prolyl hydroxylase 3 (PHD3) hydroxylates the proline residue of HIFα, mediating HIFα degradation. The von Hippel-Lindau protein (pVHL) is an E3 ligase which mediates ubiquitination and degradation of hydroxylated HIFα.

Targeting UPR branches, a potential strategy for enhancing efficacy of cancer chemotherapy.

Cancer cells are often exposed to cell intrinsic stresses and environmental perturbations that may lead to accumulation of unfolded and/or misfolded proteins in the lumen of endoplasmic reticulum (ER), a cellular condition known as ER stress. In response to ER stress, the cells elicit an adaptive process called unfolded protein response (UPR) to cope with the stress, supporting cellular homeostasis and survival. The ER stress sensors inositol requiring protein 1α (IRE1α), eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3, also called PERK), and activating transcription factor 6 (ATF6) constitute the three branches of UPR to resolve ER stress.

The tyrosine phosphatase SHP2 promotes proliferation and oxaliplatin resistance of colon cancer cells through AKT and ERK.

The SH2 domain-containing phosphatase 2 (SHP2) is a widely expressed protein tyrosine phosphatase, and it is proposed to act as an oncogenic protein. SHP2 is also engaged in drug resistance of a variety of cancers. However, the role of SHP2 in the proliferation and drug resistance of colon cancer cells remains elusive.

The non-canonical functions of HIF prolyl hydroxylases and their dual roles in cancer.

The hypoxia-inducible factor (HIF) prolyl hydroxylases (PHDs) are dioxygenases using oxygen and 2-oxoglutarate as co-substrates. Under normoxia, PHDs hydroxylate the conserved prolyl residues of HIFα, leading to HIFα degradation. In hypoxia PHDs are inactivated, which results in HIFα accumulation.