<p>MicroRNA-802 Suppresses Tumorigenesis of Colorectal Cancer via Regulating UBN2</p>

Abstract

Background: The initiation and progression of colorectal cancer (CRC) are a multistep complex process regulated by multiple factors. Previous evidence indicated that microRNA-802 (miR-802) participated in tumorigenesis of numerous solid cancers; however, the potential roles and underlying mechanisms of miR-802 in CRC still need further exploration. Methods: Quantitative real-time PCR (qRT-PCR) was employed to evaluate miR-802 levels in human CRC tissues and cell lines. In vitro proliferation, apoptosis, migration and invasion assays, and in vivo subcutaneous mouse xenograft model were utilized to examine the effects of miR-802 on the malignant behaviors of CRC cells. Then, bioinformatics prediction, dualluciferase reporter, qRT-PCR, and Western blot was conducted to confirm the downstream target of miR-802. Results: MiR-802 was frequently down-regulated in CRC tissues and cells. Further analyses showed that the low expression of miR-802 in CRC tissues was significantly correlated with tumor progression and poor patients' prognosis. Overexpression of miR-802 profoundly inhibited proliferation, migration and invasion but promoted apoptosis of CRC cells, by contrast, miR-802 silencing exhibited opposite effects in vitro. Further animal experiment demonstrated that miR-802 could suppress tumor growth via inhibiting the proliferation and promoting the apoptosis of CRC cells in vivo. Mechanistically, miR-802 functioned as a tumor suppressor through inhibiting the expression of Ubinuclein-2 (UBN2) on posttranscriptional level. Moreover, upregulation of UBN2 expression could reverse the biological effects of CRC cells induced by miR-802 overexpression. Conclusion: Our study demonstrates that miR-802 inhibits the proliferation, migration and invasion while promotes the apoptosis of CRC cells via directly suppressing UBN2 expression. These findings provide a promising biomarker and potential treatment target for CRC.

Dysfunction of miR‐802 in tumors

“…In vitro experiments also further showed that miR-802 promoted the proliferation of lung cancer cells. 35 The abnormal expression of miR-802 has been confirmed in the tumor tissues or tumor cells of 15 cancers, including TSCC, 4 OSCC, 5,6 LSCC, 8 GC, [9][10][11] CRC, [12][13][14] PC, [30][31][32] HCC, [22][23][24][25] PCa, 2,33 bladder urothelial cancer, 26 BC, 15,16 CC, [17][18][19] EOC, 20 lung cancer, [34][35][36] osteosarcoma, 27,28 and melanoma. 21 To note, the abnormal expression of miR-802 in ESCC 7 and cholesteatoma 29 has only been confirmed in tumor cells.…”

“…Subsequent experiments further revealed that miR-802 expression can regulate a series of cell behaviors, including cell proliferatio n, 2,[7][8][9]11,[13][14][15]18,[20][21][22][24][25][26]28,29,31,[33][34][35] invasion, 4,6,[11][12][13][14]17,[19][20][21]33,34,36 metastasis, 2,6,7,[11][12][13][14]17,20,21,25,26,33,34,36 apoptosis, [8][9][10]13,...…”

“…37 In CRC, low expression of miR-802 is an independent prognostic factor affecting OS in patients, and decreased expression of miR-802 is associated with the progression of CRC and poor prognosis of patients. 14 In contrast, high expression of miR-802 was significantly associated with poor OS and cancer-specific survival (CSS) of CRC. 38 However, miR-802 expression is elevated in HCC and PCa.…”

“…Some studies have also confirmed the tumor suppressor effect of miR‐802 in mouse models. Existing studies have found that the expression of miR‐802 is decreased in at least 10 cancers, including TSCC, 4 OSCC, 5 , 6 ESCC, 7 LSCC, 8 GC, 9 , 10 , 11 CRC, 12 , 13 , 14 BC, 15 , 16 CC, 17 , 18 , 19 EOC, 20 and melanoma. 21 It is worth noting that the direction of abnormal expression of miR‐802 in the other 4 tumors is inconsistent.…”

“…Subsequent experiments further revealed that miR‐802 expression can regulate a series of cell behaviors, including cell proliferation, 2 , 7 , 8 , 9 , 11 , 13 , 14 , 15 , 18 , 20 , 21 , 22 , 24 , 25 , 26 , 28 , 29 , 31 , 33 , 34 , 35 invasion, 4 , 6 , 11 , 12 , 13 , 14 , 17 , 19 , 20 , 21 , 33 , 34 , 36 metastasis, 2 , 6 , 7 , 11 , 12 , 13 , 14 , 17 , 20 , 21 , 25 , 26 , 33 , 34 , 36 apoptosis, 8 , 9 , 10 , 13 , 18 , ...…”