miR-517a is an independent prognostic marker and contributes to cell migration and invasion in human colorectal cancer

Abstract

Abstract. Colorectal cancer (CRC) is a highly invasive tumor that is frequently associated with distant metastasis, which is the primary cause of poor prognosis. However, the mechanisms of metastasis remain poorly understood. MicroRNAs (miRNAs/miRs) have been considered to be implicated in CRC progression. In particular, miR-517a is proposed as a novel tumor-associated miRNA and has a potential role in tumor metastasis. The expression of miR-517a in CRC specimens was detected by reverse transcription-quantitative polymerase chain reaction. Transwell assays were performed to determine the migration and invasion of CRC cells. The putative target genes of miR-517a were disclosed using publicly available databases and western blot analysis. The present study identified that the expression of miR-517a was significantly higher in CRC tissues as compared with adjacent non-tumor tissues. Clinical analysis indicated that increased expression of miR-517a was correlated with poor prognostic features and poor long-term survival of CRC patients. In vitro evidences demonstrated that downregulation of miR-517a inhibited cell migration and invasion in HCT-116 cells. By contrast, upregulation of miR-517a increased the number of migrated and invaded SW480 cells. Notably, miR-517a expression was inversely regulated by forkhead box J3 (FOXJ3) abundance in CRC cells. Furthermore, an inverse correlation between miR-517a and FOXJ3 expression was observed in CRC tissues. In conclusion, miR-517a appears to be an independent prognostic marker for predicting survival of CRC patients, and may promote cell migration and invasion by inhibiting FOXJ3.

Tissue micro-RNAs associated with colorectal cancer prognosis: a systematic review

“…A total of 32 studies demonstrated the association between the downregulation of 32 miRs and the presence of lymph node metastasis such as miR-6852 106 , miR-302c 67 , miR-466 68 , miR-340 69 , miR-944 71 , miR-30d 72 , miR-22 50 , miR-296 73 , miR-199b 47 , let-7a-5p 98 , miR-132 99 , miR-497 107 , miR-206 100 , miR-128 75 , miR-154 78 , miR-149 79 , miR-24-3p 54 , miR-15a 34 , miR-16 34, 36 , miR-193a-5p 108 , miR-100 81 , miR-133a 41 , miR-205 109 , miR-335 82 , miR-378 101 , miR-218 83 , miR-138 110 , miR-625 111 , miR-212 112 , miR-195 113 , miR-133b 37 and miR-30c 103 . Other 30 studies verified the upregulation of miR-1296 84 , miR-200c 114 , miR-21 26, 29 , miR-130a 85 , miR-7 55 , miR-96 86 , miR-1260b 115 , miR-517a 87 , miR-106b 88 , miR-320e 89 , miR-196a 57 , miR-196b 57 , miR-376a 116 , miR-720 91 , miR-494 61 , miR-630 92 , miR-181a 31 , miR-20a 62 , miR-210 93 , miR-182 43, 44 , miR-25 94 , miR-191 95 , miR-183 46 , miR-199a-3p 117 , miR-429 105 , miR-92a 96 , miR-10b 118 , miR-155 30 and miR-552 97 associated with the presence of lymph node metastasis.…”

“…Two studies demonstrated the upregulation of miR-182 43, 44 associated with advanced TNM stage and others 22 studies pointed 23 different upregulated miRs associated with advanced TNM stage. In detail, miR-1296 84 , miR-888 64 , miR-21 29 , miR-130a 85 , miR-7 55 , miR-96 86 , miR-20a-5p 63 , miR-517a 87 , miR-106b 88 , miR-320e 89 , miR-592 90 , miR-196a 57 , miR-196b 57 , miR-720 91 , miR-133a 42 , miR-630 92 , miR-181a 31 , miR-210 93 , miR-25 94 , miR-191 95 , miR-92a 96 , miR-31 59 and miR-552 97 have been reported.…”

“…The downregulation of miR-466 68 , miR-944 71 , miR-30d 72 , miR-22 49, 50 , miR-296 73 , miR-140-5p 119 , miR-199b 48 , miR-155-5p 77 , miR-99b-5p 120 , miR-154 78 , miR-149 79 , miR-96-5p 121 , miR-133b 38, 39 , miR-126 40 , miR-138 110 , miR-625 111 and miR-212 112 was associated with the presence of distant metastasis in 19 studies. The upregulation of miR-888 64 , miR-20a-5p 63 , miR-517a 87 , miR-320e 89 , miR-592 90 , miR-720 91 , miR-494 61 , miR-133a 42 , miR-210 38 , miR-630 92 , miR-17-5p 60 , miR-181a 31 , miR-25 94 , miR-191 95 , miR-183 46 , miR-224 52 , miR-199a-3p 117 , miR-92a 96 , miR-372 122 , miR-185 39 and miR-21 26, 28, 30 was associated with the presence of distant metastasis in 23 studies.…”

“…Among the evaluated studies, 49 demonstrated the downregulation of miR-199b 47, 48 , miR-6852 106 , miR-302c 67 , miR-466 68 , miR-650 123 , miR-196b-5p 70 , miR-944 71 , miR-30d 72 , miR-296 73 , miR-187 124 , let-7a-5p 98 , miR-132 99 , miR-206 100 , miR-148a 125 , miR-33b 76 , miR-99b-5p 120 , miR-154 78 , miR-217 126 , miR-149 79 , miR-194 80 , miR-7 56 , miR-24-3p 54 , miR-29b 127 , miR-15a 34 , miR-16 34, 36 , miR-204-5p 128 , miR-96-5p 121 , miR-193a-5p 108 , miR-100 81 , miR-133a 41 , miR-139-5p 129 , miR-124-5p 130 , miR-335 82 , miR-378 101 , miR-126 40 , miR-378a-3p 58 , miR-378a-5p 58 , miR-218 83 , miR-138 110 , miR-625 111 , miR-212 112 , miR-124 131 , miR-22 49 , miR-133b 39 , miR-193a-3p 104 , miR-195 113 and miR-30c 103 associated with worse prognosis (lower overall survival) of CRC patients. Fifty-six studies identified the upregulation of miR-181a 31–33 , miR-182 43, 44 , miR-1296 84 , miR-888 64 , miR-28-5p 132 , miR-183 45, 46 , miR-200c 114 , miR-34a 133 , miR-15a-5p 134 , miR-181c 135 , miR-24-3p 53 , miR-16 35 , miR-7 55 , miR-96 86 , miR-1260b 115 , miR-20a-5p 63 , miR-517a 87 , miR-503 136 , miR-106b 88 , miR-211 137 , miR-320e 89 , miR-592 90 , miR-196a 57 , miR-196b 57 , miR-376a …”

Non‐digestible carbohydrates supplementation increases miR‐32 expression in the healthy human colorectal epithelium: A randomized controlled trial

“…Furthermore, some of these miRNAs may have potential for development as biomarkers in investigations of the protective or detrimental effects of dietary factors, such as red meat and dietary fibre, on CRC risk. For example, miR‐1287 and miR‐517 are upregulated in CRC tissue and miR‐133b (which has been proposed to be a tumor suppressor) is downregulated in SW‐620 and HT‐29 colon cells . In addition, miR‐135a has been identified as a biomarker of CRC in serum and was downregulated by butyrate and trichostatin A, another HDACi, in LT97 colon adenoma cells.…”