Exploiting E3 ubiquitin ligases to reeducate the tumor microenvironment for cancer therapy.

Tumor development relies on a complex and aberrant tissue environment in which cancer cells receive the necessary nutrients for growth, survive through immune escape, and acquire mesenchymal properties that mediate invasion and metastasis. Stromal cells and soluble mediators in the tumor microenvironment (TME) exhibit characteristic anti-inflammatory and protumorigenic activities. Ubiquitination, which is an essential and reversible posttranscriptional modification, plays a vital role in modulating the stability, activity and localization of modified proteins through an enzymatic cascade.

Novel insights into the SPOP E3 ubiquitin ligase: From the regulation of molecular mechanisms to tumorigenesis.

Ubiquitin-mediated protein degradation is the primary biological process by which protein abundance is regulated and protein homeostasis is maintained in eukaryotic cells. Speckle-type pox virus and zinc finger (POZ) protein (SPOP) is a typical substrate adaptor of the Cullin 3-RING ligase (CRL3) family; it serves as a bridge between the Cullin 3 (Cul3) scaffold protein and its substrates. In recent years, SPOP has received increasing attention because of its versatility in its regulatory pathways and the diversity of tumor types involved.

Transcriptional regulation and ubiquitination-dependent regulation of HnRNPK oncogenic function in prostate tumorigenesis.

Background: Heterogeneous nuclear ribonucleoprotein K (HnRNPK) is a nucleic acid-binding protein that regulates diverse biological events. Pathologically, HnRNPK proteins are frequently overexpressed and clinically correlated with poor prognosis in various types of human cancers and are therefore pursued as attractive therapeutic targets for select patients. However, both the transcriptional regulation and degradation of HnRNPK in prostate cancer remain poorly understood.

The putative tumour suppressor miR-1-3p modulates prostate cancer cell aggressiveness by repressing E2F5 and PFTK1.

Background: Previous studies report that miR-1-3p, a member of the microRNA-1 family (miR-1), and functions as a tumor suppressor in several different cancers. However, little is known regarding the biological role and intrinsic regulatory mechanisms of miR-1-3p in prostate cancer (PCa).

Methods: In this study, the expression levels of miR-1-3p were first examined in PCa cell lines and tumor tissues by RT-qPCR and bioinformatics.

miR-3619-5p inhibits prostate cancer cell growth by activating CDKN1A expression.

Recent studies have shown that miRNAs have potent abilities to activate gene expression by targeting promoter elements, a phenomenon known as RNA activation (RNAa). In the present study, we identified a new endogenous miR-3619-5p which was decreased in prostate cancer tissues and cells compared to corresponding normal controls. Moreover, overexpression of miR-3619-5p readily induced CDKN1A gene expression by directly targeting the putative site in the promoter.

Genetic variants in PI3K/AKT pathway are associated with severe radiation pneumonitis in lung cancer patients treated with radiation therapy.

PI3K/AKT pathway plays important roles in inflammatory and fibrotic diseases while its connection to radiation pneumonitis (RP) is unclear. In this study, we explored the associations of genetic variants in PI3K/AKT pathway with RP in lung cancer patients with radiotherapy. Two hundred and sixty one lung cancer patients with radiotherapy were included in this prospective study (NCT02490319) and genotyped by MassArray and Sanger Sequence methods.

HPV seropositivity joints with susceptibility loci identified in GWASs at apoptosis associated genes to increase the risk of Esophageal Squamous Cell Carcinoma (ESCC).

Background: We previously showed that human papillomavirus (HPV) serostatus was not an independent risk factor for esophageal squamous cell carcinoma(ESCC) in nonsmokers and nondrinkers; however, HPV increased the risk in smokers.

Methods: Here we investigated possible interactions between HPV16 serostatus and three susceptibility loci identified in GWASs at apoptosis associated genes with regard to risk of ESCC in a case-control study of 313 patients with ESCC and 314 healthy controls. The loci (CHK2 rs738722, C12orf51 rs2074356, and PLCE1 rs2274223) were genotyped, and the presence or absence of HPV16 in serum was measured by ELISA.

Lack of association between interleukin-4 -524C>T polymorphism and colorectal cancer susceptibility.

Interleukin-4 (IL-4) -524C > T polymorphism has been implicated to alter the risk of colorectal cancer (CRC), but the results are controversial. The objective of this study was to quantitatively evaluate the association between IL-4 -524C > T polymorphism and CRC risk. A comprehensive search was conducted to identify all eligible studies of IL-4 -524C > T polymorphism and CRC risk.

Associations between single-nucleotide polymorphisms in the PI3K-PTEN-AKT-mTOR pathway and increased risk of brain metastasis in patients with non-small cell lung cancer.

Purpose: Non-small cell lung cancer (NSCLC) metastasizes fairly often to the brain, but identifying which patients will develop brain metastases is problematic. The phosphoinositide 3-kinase (PI3K)-AKT-mTOR signaling pathway is important in the control of cell growth, tumorigenesis, and cell invasion. We hypothesized that genotype variants in this pathway could predict brain metastasis in patients with NSCLC.

SNPs in the TGF-β signaling pathway are associated with increased risk of brain metastasis in patients with non-small-cell lung cancer.

Purpose: Brain metastasis (BM) from non-small cell lung cancer (NSCLC) is relatively common, but identifying which patients will develop brain metastasis has been problematic. We hypothesized that genotype variants in the TGF-β signaling pathway could be a predictive biomarker of brain metastasis.

Patients And Methods: We genotyped 33 SNPs from 13 genes in the TGF-β signaling pathway and evaluated their associations with brain metastasis risk by using DNA from blood samples from 161 patients with NSCLC.

Association of estrogen receptor beta variants and serum levels of estradiol with risk of colorectal cancer: a case control study.

Background: Endogenous estrogens may play a vital role in colorectal tumorigenesis. Estrogen receptor beta is the predominant subtype which mediates the biological effect of estrogens, while loss of expression of estrogen receptor beta has been indicated as a common step in the development of colorectal cancer (CRC). Epidemiological studies have revealed several functional polymorphisms of estrogen receptor beta (ESR2) for cancer risk, but relevant study in CRC is limited, particularly in men.

Colorectal cancer screening: comparison of transferrin and immuno fecal occult blood test.

Aim: To evaluate the sensitivity and specificity of transfesrrin dipstick test (Tf) in colorectal cancer (CRC) screening and precancerous lesions screening.

Methods: Eight hundreds and sixty-one individuals at high-risk for CRC were recruited. Six hundreds and eleven subsequently received the three fecal occult blood tests and colonoscopy with biopsy performed as needed.