Hypermethylated miR-424 in Colorectal Cancer Subsequently Upregulates VEGF

Abstract

Purpose Colorectal cancer (CRC) is the second leading cause of death from cancer in adults. Recent advances have shown that cancer cells can have some epigenetic changes involved in all stages of cancer. It has also been shown that miR-424 acts as gene expression regulators in many biological processes, including angiogenesis with mediators such as VEGF. In the current study, to identify the potential role of miR-424 in colorectal cancer progression, methylation status of miR-424 promoter region and its expression level have been evaluated. Besides, the correlation between VEGF level and miR-424 expression level has been assessed. Methods Methylation status miR-424 promoter was assessed using methylation-speci c polymerase chain reaction (MSP). The expression level of miR-424 in human colorectal cancer tissue was analyzed by quantitative PCR. HCT116 cell line was selected to evaluate the correlation between the miR-424 expression level and the promoter's methylation status. VEGF expression, one out of mir-424 targets involved in angiogenesis and cancer progression, was measured by western blot analysis in the pairs of cancer tissues and their adjacent tissues. Results Our results have revealed that the promoter region of miR-424 is methylated in cancer cells compared to normal cells, leading to down-regulation of miR-424 in the colorectal cancer tissues compared to the normal tissues. Also, we found that the expression protein's level of VEGF in the tumor cells increased compared with normal tissues. Conclusion The present study suggests that hypermethylation downregulates miR-424. VEGF expression is upregulated with decreased miR-424 in colorectal cancer, which results in cancer progression.

MiRNA-424-5p Suppresses Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma and Attenuates Expression of O-GlcNAc-Transferase

“…Similarly, in bladder cancer, tumor progression is regulated by DMNT dependent methylation of the CpG island promoter [20]. Reduced expression of miR-424-5p was also seen in ovarian cancer [21] and colorectal cancer [22] cells, stemming from increased methylation of the miR-424-5p promoter. Our present studies on the impact of 5 Aza on miR-424-5p expression support the idea that reduced miR-424-5p expression in aggressive stage I ccRCC stems from increased DNA methylation.…”

“…Methylation of the miR-424-5p CpG island promoter has been identified as a cause of reduced expression of miR-424-5p in numerous other cancer types [19][20][21][22]. However, the impact of methylation on expression of miR-424-5p in ccRCC has not yet been established.…”

“…Similarly, miR-424-5p has been demonstrated to play a tumor suppressor role in a wide range of other cancers [13][14][15][16][17][18], exerting its phenotypic impact on the cell by inhibiting proliferation, migration, and invasion while inducing apoptosis. Reduced expression of miR-424-5p has been connected to an increase in methylation of the miR-424 promoter CpG island in several cancer types [19][20][21][22]. Conversely, high expression of miR-424-5p has also been associated with ccRCC of high stage, grade, and progression [8], and miR-424-5p has been demonstrated as an oncogene in other cancers [23,24].…”

Integrated Analysis of Ulcerative Colitis Revealed an Association between PHLPP2 and Immune Infiltration

“…The impact of miR-424 on UC is indistinctive. miR-424 has been studied mostly in tumors and is aberrantly expressed in multiple cancers such as renal clear cell carcinomas [25], colon cancer [26], chronic leukemia [27], pancreatic cancer [28], and ovarian cancer [29]. Moreover, miR-424 plays a dual role as it acts both as a tumor suppressor [30,31] and as a cancer promoter [28,32].…”

The Role and Interactions of Programmed Cell Death 4 and its Regulation by microRNA in Transformed Cells of the Gastrointestinal Tract

“…The disparity between miRNA-424 having properties of either an oncomir or tumour suppressor is also seen in GC cell lines ( 229 , 230 , 232 , 234 ). Similarly, investigations examining miRNA-424 in colorectal cancer have found the microRNA to be either pro- ( 235 – 237 ) or anti-oncogenic ( 238 – 240 ).…”