MicroRNA-1296 Facilitates Proliferation, Migration And Invasion Of Colorectal Cancer Cells By Targeting SFPQ

Abstract

MicroRNAs (miRNAs) are involved in cancer genesis and progression via acting as tumor suppressors or oncogenes. Previous studies report that miR-1296 shows upregulation in both colorectal cancer (CRC) tissues and plasma samples. However, the accurate clinical significance of miR-1296 and its role in CRC have not been well investigated. The aim of the present study was to disclose the aberrant expression, clinical significance, and the relevant biological function of miR-1296 in CRC. We found a marked upregulation of miR-1296 expression in CRC tissues compared to tumor-adjacent tissues. MiR-1296 overexpression was detected in five CRC cell lines (HCT116, Caco2, HT29, SW620 and SW480). High miR-1296 level was remarkably correlated with tumor size (>5cm), lymph node metastasis and TNM stage (III+IV). Notably. High miR-1296 expression was identified as a predictive factor for poor prognosis of CRC patients by survival analysis. MiR-1296 knockdown inhibited proliferation, migration, invasion capacities of HCT116 and SW480 cells in vitro. Moreover, miR-1296 silencing restrained the growth of CRC cells in vivo. Splicing factor proline and glutamine rich (SFPQ), a novel RNA binding protein, was identified as a direct target gene of miR-1296 in CRC. Downregulation of SFPQ expression was inversely associated with miR-1296 expression in CRC tissues. The Cancer Genome Atlas (TCGA) data revealed the prognostic value of dysregulated SFPQ in CRC patients. Interestingly, our findings established that the oncogenic role of miR-1296 was at least partially mediated by SFPQ in CRC cells. Collectively, these data indicate that miR-1296 accelerates CRC progression possibly by targeting SFPQ and may serve as a potential predictive factor and therapeutic target for CRC.

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

“…Tumor growth was associated with the downregulation of 14 miRs reported in 13 studies: miR-302c 67 , miR-466 68 , let-7a-5p 98 , miR-132 99 , miR-206 100 , miR-33b 76 , miR-154 78 , miR-194 80 , miR-100 81 , miR-378 101 , miR-378a-3p 58 , miR-378a-5p 58 , miR-148b 102 and miR-30c 103 . Ten studies verified the upregulation of miR-1296 84 , miR-193a-3p 104 , miR-592 90 , miR-720 91 , miR-210 93 , miR-182 44 , miR-429 105 ,miR-125b 66 and miR-21 26, 28 associated with tumor growth as well.…”

“…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.…”

“…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 …”

Cellular and molecular architecture of hematopoietic stem cells and progenitors in genetic models of bone marrow failure

“…To our knowledge, SFPQ was previously reported to be mutated only in 1 subject with AML (67). A recent study suggested downregulation of SFPQ by miRNA-1296 in colorectal cancer as a mechanism for cell proliferation (68). The published mutation in a patient with AML was described as nonsynonymous without further details.…”