ABSTRACT
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.
Subject(s)
Agrin/metabolism , Rectal Neoplasms/metabolism , Signal Transduction , Wnt Proteins/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , Disease Progression , Gene Expression Regulation, Neoplastic , Humans , Neoplasm Invasiveness , Prognosis , RNA, Small Interfering/metabolism , Up-Regulation , Wnt Signaling PathwayABSTRACT
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.
ABSTRACT
[This corrects the article DOI: 10.1515/biol-2020-0031.].
