Agrin promotes the proliferation, invasion and migration of rectal cancer cells via the WNT signaling pathway to contribute to rectal cancer progression.

Rectal cancer is the most common malignant tumor in the digestive system with rapidly metastasis and highly recurrence. Agrin (AGRN) is a proteoglycan involving in a large number of human cancers. However, how AGRN regulates the progression of rectal cancer remains largely unknown. We aimed to determine the biological role of AGRN and its mechanism in rectal cancer. AGRN expression in rectal cancer tissues was detected based on TCGA. The survival curve was plotted using the Kaplan-Meier method. qRT-PCR and western blot were utilized to examine the expression level of AGRN in cells. Cell proliferation, clonogenic ability, invasion, and migration of rectal cancer cells were analyzed by CCK-8, colony formation and transwell experiments. GSEA was employed for the analysis of the potential pathways-related with AGRN in rectal cancer. The activity of WNT pathway was determined by western blot. AGRN expression was dramatically increased in rectal cancer, and its up-regulation was associated with poorer prognosis of rectal cancer patients. AGRN expression was an independent factor for the prognosis of rectal cancer. AGRN inhibition suppressed rectal cancer cell growth, invasion, and migration, whereas AGRN overexpression facilitated these behaviors of rectal cancer cells in vitro. Mechanistically, WNT signaling pathway was enriched in high AGRN-expressing patients with rectal cancer. AGRN elevated the activity of WNT pathway through increasing Cyclin D1, C-Myc, p-GSK-3ß, and p-ß-catenin expression. Our present study indicated that AGRN might function as an oncogenic indicator in rectal cancer via activating the WNT pathway, which would help develop optimized therapeutic therapies for rectal cancer.

MYL6B drives the capabilities of proliferation, invasion, and migration in rectal adenocarcinoma through the EMT process.

OBJECTIVE: This study was designed to explore the biological significance of myosin light chain 6B (MYL6B) in rectal adenocarcinoma. METHODS: Profiles on the Oncomine dataset, GEPIA website, and UALCAN-TCGA database were searched to assess the MYL6B expression level in rectal adenocarcinoma tissues and normal tissues. After MYL6B knockdown using siRNA strategy, cell counting kit-8 (CCK-8) and transwell assays were conducted to measure cell proliferation, migration and invasion, respectively. Flow cytometry analysis was conducted to assess cell apoptosis. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot were performed to detect the expression level of mRNAs and proteins. RESULTS: The data showed that overexpression of MYL6B was observed in rectal adenocarcinoma tissues and correlated with a poor prognosis of patients. Functional in vitro experiments revealed that MYL6B knockdown could inhibit proliferation, migration, and invasion of rectal adenocarcinoma cells, while promote cell apoptosis. Moreover, western blot analysis suggested that increased expression of E-cadherin and decreased expression of N-cadherin and Vimentin were induced by si-MYL6B. CONCLUSION: In summary, this study elaborated on the promoting effect of MYL6B in rectal adenocarcinoma progression, thus providing novel insight for strategies of clinical diagnosis and drug application in the future clinical study.

Erratum to "MYL6B drives the capabilities of proliferation, invasion, and migration in rectal adenocarcinoma through the EMT process".

[This corrects the article DOI: 10.1515/biol-2020-0031.].

Partner of Sld five 3: a potential prognostic biomarker for colorectal cancer.

BACKGROUND: Partner of Sld five 3 (PSF3) is a member of the evolutionarily conserved heterotetrameric complex "Go-Ichi-Ni-San" (GINS), which consists of SLD5, PSF1, PSF2, and PSF3. Previous studies have suggested that some GINS complex members are upregulated in cancer, but the status of PSF3 expression in colorectal cancer has not been investigated. METHODS: We investigated the status of PSF3 expression in 137 consecutive resected colorectal caners by quantitative reverse-transcription polymerase chain reaction. Univariable and multivariable Cox regression analyses were performed to assess independent prognostic factors for overall survival in colorectal cancer. RESULTS: In 137 restected colorectal cancer samples, median messenger RNA (mRNA) expression levels of PSF3 were significantly higher in tumor tissues (1.35 × 10(-3), range 2.88 × 10(-4) to 3.16 × 10(-2)) than in adjacent normal tissues (2.94 × 10(-4), range 5.48 × 10(-5) to 1.27 × 10(-3)) (P < 0.05). Moreover, high expression of PSF3 in tumor tissues was associated with shorter disease-free survival and overall survival. When analyzed with a Cox regression model, the PSF3 expression was an independent prognostic factor for overall survival. In addition, in patients with early stage (stage I and II) colorectal cancer, the overall survival rate of the high PSF3 expression group was significantly lower than that of the low PSF3 expression group (P < 0.001). CONCLUSIONS: The PSF3 expression plays an important role in the progression of colorectal cancer and acts as a factor significantly affecting the prognosis of patients. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_217.

Association between miR-27a genetic variants and susceptibility to colorectal cancer.

BACKGROUND: MicroRNAs (miRNAs) are short, non-coding RNAs that negatively regulate target genes. A single nucleotide polymorphism (SNP) in a miRNA sequence may alter miRNA expression and/or maturation, which was proposed to associate with the development and progression of cancer. The rs895819 polymorphism, located in the terminal loop of pre-miR-27a, has been reported to have relevance to several cancers. In this study, we investigated the possibility of association between polymorphism in rs895819 and susceptibility to colorectal cancer (CRC). METHODS: We identified a single SNP, rs895819 in pre-miR-27a, for further investigation, were determined in 205 CRC patients and 455 healthy controls. RESULTS: When taking the AA genotype as a reference, we found that AG genotype was not statistically significantly associated with the risk of CRC (AG vs. AA, OR 1.245, 95% CI: 0.806 - 1.923). However, the GG genotype was significantly associated with risk of CRC (GG vs. AA, OR 1.599, 95% CI: 1.052 - 2.430). In the AG + GG vs GG group, no significant difference was detected (OR 1.424, 95% CI, 0.974 - 1.801). GG genotype and G allele was associated with an increased risk of metastasis in this study (P < 0.001 and P = 0.003, respectively). CONCLUSIONS: This study found significant association between rs895819 polymorphism in pre-miR-27a and CRC risk. Population-based studies with large number of subjects and long-term follow-up are needed to verify the association of miR-27a polymorphism with CRC susceptibility and severity. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2061490734125077.