Colon cancer is one of the most common types of cancer worldwide. Methotrexate (MTX) is a chemotherapy drug used for the treatment of multiple types of cancer, such as colon and breast cancer. To determine the effects of MTX treatment on colorectal adenocarcinoma cell lines, a microRNA (miRNA) microarray was used to detect miRNA expression profiles of HT-29 colorectal adenocarcinoma MTX-resistant cells and their parental cells. The results demonstrated that 641 genes and 43 miRNAs were differentially expressed between HT-29 MTX-sensitive cells and MTX-resistant cells. In addition, 12 miRNAs and their co-expressed genes were highly correlated in MTX treatment, and one of the identified miRNAs, miR-770-5p, was studied in subsequent experiments. Upregulation of miR-770-5p significantly decreased the sensitivity of HT-29 cells to MTX. Using bioinformatics software, homeodomain-interacting protein kinase 1 (HIPK1) was identified to be a putative target gene of miR-770-5p, which was confirmed by a luciferase reporter assay. Downregulation of miR-770-5p target gene HIPK1 significantly decreased the sensitivity of HT-29 cells to MTX. These results suggest that miR-770-5p may be involved in the regulation of colon cancer resistance to MTX by regulating the expression of the target gene HIPK1.
Open splenectomy is an effective treatment with less complications for the management of ITP. Lower preoperative minimum platelet count associated with successful OS at 5 yrs.
BACKGROUND: The role of ELAPOR1 has been evaluated in several cancers but has not been elucidated in colorectal cancer (CRC). OBJECTIVE: To investigate the role of ELAPOR1 in CRC. METHODS: In the present study, the correlation between ELAPOR1 and survival of CRC patients in TCGA-COAD-READ datasets was predicted, and the difference in ELAPOR1 expression between tumor and normal tissues was analyzed. ELAPOR1 expression in CRC tissues was measured by immunohistochemistry. Then, ELAPOR1 and ELAPOR1-shRNA plasmids were constructed and transfected into SW620 and RKO cells. The effects were assessed by CCK-8, colony formation, transwell, and wound healing assays. Transcriptome sequencing and bioinformatics analysis were performed on the genes before and after ELAPOR1 overexpression in SW620 cells; the differentially expressed genes were substantiated by real-time quantitative reverse transcription PCR. RESULTS: High level of ELAPOR1 is associated with favorable disease-free survival and overall survival. Compared to normal mucosa, ELAPOR1 is lower in CRC. Moreover, ELAPOR1 overexpression significantly inhibits cell proliferation and invasion in vitro in SW260 and RKO cells. Conversely, ELAPOR1-shRNA promotes CRC cell proliferation and invasion. Among the 355 differentially expressed mRNAs identified, 234 were upregulated and 121 were downregulated. Bioinformatics indicated that these genes are involved in receptor binding, plasma membrane, negative regulation of cell proliferation, as well as common cancer signaling pathways. CONCLUSIONS: ELAPOR1 plays an inhibitory role in CRC and may be used as a prognostic indicator and a potential target for treatment.
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