RETRACTED ARTICLE: microRNA -140-5p inhibits colorectal cancer invasion and metastasis by targeting ADAMTS5 and IGFBP5

Abstract

BackgroundColorectal cancer (CRC) is one of the most common malignancies in the world. microRNA-140-5p (miR-140) has been shown to be involved in cartilage development and osteoarthritis (OA) pathogenesis. Some contradictions still exist concerning the role of miR-140 in tumor progression and metastasis, and the underlying mechanism is uncertain.MethodsImmunohistochemistry was performed to determine the expressions of ADAMTS5 and IGFBP5 in CRC tissues. Human CRC cell lines HCT116 and RKO were transfected with miR-140 mimic, inhibitor, or small interfering RNA (siRNA) against ADAMTS5 or IGFBP5, respectively, using oligofectamine or lipofectamine 2000. Scratch-wound assay and transwell migration and invasion assays were used to evaluate the effects of miR-140 on the capabilities of migration and invasion. The levels of miR-140 and ADAMTS5 and IGFBP5 mRNA were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was performed to examine the expression of ADAMTS5 and IGFBP5 proteins.ResultsmiR-140 was significantly reduced, whereas ADAMTS5 and IGFBP5 were upregulated, in the human CRC tissues compared to the corresponding normal colorectal mucosa. miR-140 downregulation and ADAMTS5 or IGFBP5 overexpression were associated with the advanced TNM stage and distant metastasis of CRC. There was a reverse correlation between miR-140 levels and ADAMTS5 and IGFBP5 expression in CRC tissues. ADAMTS5 and IGFBP5 were downregulated by miR-140 at both the protein and mRNA levels in the CRC cell lines. The gain-of- and loss-of-function studies showed that miR-140 inhibited CRC cell migratory and invasive capacities at least partially via downregulating the expression of ADAMTS5 and IGFBP5.ConclusionsThese findings suggest that miR-140 suppresses CRC progression and metastasis, possibly through downregulating ADAMTS5 and IGFBP5. miR-140 might be a potential therapeutic candidate for the treatment of CRC.

MicroRNAs: Potential candidates for diagnosis and treatment of colorectal cancer

“…These results indicated that up regulation of miR‐140‐5p could inhibit metastasis and invasive effect of CRC cells via down regulation of ADAMTS5, IGFBP5. These data suggested that this miRNAs might be applied as a new therapeutic biomarkers in patients with CRC (Yu et al, ). Table illustrates a large number of miRNAs and their targets that are involve in CRC pathogenesis and could be used as diagnostic, prognostic and therapeutic biomarkers in this disease.…”

“…IGFBP5 is an important protein which play key role in cell growth and survival and up regulation of it involve in cancer progression (Baxter, ). Yu et al () indicated that miR‐140‐5p is capable to affect the progression of CRC cells via targeting ADAMTS5, IGFBP5. Down regulation of miR‐140‐5p and up regulation of ADAMTS5, IGFBP5 are observed in CRC samples which are associated with metastasis and advanced stages in these patients.…”

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

“…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.…”

MicroRNA‐140 inhibit prostate cancer cell invasion and migration by targeting YES proto‐oncogene 1

“…[5][6][7] Functionally, many studies demonstrated that miRNAs participated in numerous important cellular processes. [11][12][13] In addition, miR-140 overexpression was found to suppress the proliferation, migration in some cells, including cancer cells. 9,10 Furthermore, some previous studies revealed that miRNAs could inhibit the proliferation capacities of some types of cancer cells significantly.…”

“…9,10 Furthermore, some previous studies revealed that miRNAs could inhibit the proliferation capacities of some types of cancer cells significantly. [11][12][13] In addition, miR-140 overexpression was found to suppress the proliferation, migration in some cells, including cancer cells. [14][15][16] However, the direct evaluation of the expression and the biological roles of microRNA-140 (miR-140) in PCa is still rare.…”