Diagnostic Value Investigation and Bioinformatics Analysis of miR-31 in Patients with Lymph Node Metastasis of Colorectal Cancer

Abstract

Colorectal cancer (CRC) is one of the most frequent cancers occurring in developed countries. Distant CRC metastasis causes more than 90% of CRC-associated mortality. MicroRNAs (miRNAs) play a key role in regulating tumor metastasis and could be potential diagnostic biomarkers in CRC patients. This study is aimed at identifying miRNAs that can be used as diagnostic biomarkers for CRC metastasis. Towards this goal, we compared the expression of five miRNAs commonly associated with metastasis (i.e., miR-10b, miR-200c, miR-155, miR-21, and miR-31) between primary CRC (pCRC) tissues and corresponding metastatic lymph nodes (mCRC). Further, bioinformatics analysis of miR-31 was performed to predict target genes and related signaling pathways. Results showed that miR-31, miR-21, miR-10b, and miR-155 expression was increased to different extents, while miR-200c expression was lower in mCRC than that in pCRC. Moreover, we found that the level of both miR-31 and miR-21 was notably increased in pCRC when lymph node metastasis (LNM) was present, and the increase of miR-31 expression was more profound. Hence, upregulated miR-31 and miR-21 expression might be a miRNA signature in CRC metastasis. Moreover, we detected a higher miR-31 level in the plasma of CRC patients with LNM compared to patients without LNM or healthy individuals. With the bioinformatics analysis of miR-31, 121 putative target genes and transition of mitotic cell cycle and Wnt signaling pathway were identified to possibly play a role in CRC progression. We next identified seven hub genes via module analysis; of these, TNS1 was most likely to be the target of miR-31 and had significant prognostic value for CRC patients. In conclusion, miR-31 is significantly increased in the cancer tissues and plasma of CRC patients with LNM; thus, a high level of miR-31 in the plasma is a potential biomarker for the diagnosis of LNM of CRC.

High miR-31-5p expression promotes colon adenocarcinoma progression by targeting TNS1

“…To elucidate the potential mechanism of miR-31-5p involvement in COAD, a computational target prediction was performed, which identified a pivotal miR-31-5p target gene, TNS1, which is downregulated in COAD patients and closely correlated with COAD progression. This is consistent with a recent study that found that TNS1 level was negatively correlated with miR-31 in COAD tumor tissues [31]. TNS1 is a key component of specialized cellular adhesions that bind to extracellular fibronectin fibrils [32].…”

Circ_0026344 overexpression inhibits the migration, invasion, and enhances apoptosis of colorectal cancer cells by sponging miR-31

“…Consistent with the report above, our results in this study also discovered that miR-31 was high-expressed in CRC tissues. What's more, miR-31 is proved to be correlated to the metastasis of CRC and can regulate autophagy, proliferation, and chemoresistance of CRC cells (16,29,30). Similarly, in this study, the results con rmed that miR-31 overexpression not only promoted the migration, invasion, and suppressed the apoptosis of CRC cells but also counteracted the effect of circ_0026344.…”

“…In particular, circ-ITGA7 inhibits the proliferation of CRC cells by sponging miR-3187-3p (14), circ_0009361 acts as a sponge of miR-582 to inhibit the processes of CRC (8), circ_0000523 modulates the proliferation and apoptosis of CRC cells through acting as a sponge of miR-31 (13). MiR-31, highly expressed in CRC, is widely proved that it is correlated to the metastasis of CRC and has a high value in CRC diagnosis (15,16). Whether circ_0026344 had an effect on CRC by sponging miR-31 needs further exploration and veri cation.…”

Construction and Analysis of Survival-Associated Competing Endogenous RNA Network in Lung Adenocarcinoma

“…TNS1 negatively regulates tumour migration and invasion, and its high expression is associated with longer metastasis-free survival in breast cancer [ 56 ]. Moreover, higher expression of TNS1 is associated with worse prognosis in colon adenocarcinoma [ 57 ]. In this study, we observed that TNS1 was downregulated in LUAD tissues and that higher expression was associated with better prognosis ( Figure 9(d) ).…”