miR-19b promotes tumor growth and metastasis via targeting TP53

Abstract

Tumor suppressor TP53 (or p53) is one of the most important regulators in numerous physiological and pathological processes. Recently, the miRNA-mediated post-transcription regulation of p53 has been studied. However, systematic studies of miRNA targeting sites within the p53 gene are still a challenging task. Here, we developed a dual-color assay capable of identifying miRNA targeting sites in a certain gene, specifically p53, in a simple, direct, and robust manner. Results showed that p53 was a direct and critical target of miR-19b, but not miR-19a, regardless of sequence similarity. Overexpression of miR-19b observed in human cancer cells can diminish p53 protein levels and, subsequently, downstream components such as Bax and p21. This miR-19b-mediated p53 reduction was shown to promote cell cycle, cell migration or invasion, and repress senescence and apoptosis in vitro. Further investigation revealed that miR-19b controls tumor growth and metastasis in vivo. Therefore, it is possible that miR-19b antagomirs or sponges could be developed as therapeutic agents against tumor development.

MicroRNA-19 triggers epithelial–mesenchymal transition of lung cancer cells accompanied by growth inhibition

“…42,[49][50][51][52][53][54][55][56][57] In addition, miR-19 upregulation was observed in various cancers including lung cancer, and correlated with tumor metastasis and/or poor prognosis of cancer patients. [11][12][13][14][15]18 Given that miRNAs primarily function through inhibiting the translation of their mRNA targets, we propose that miR-19 might be a negative regulator for PTEN, which has been reported by other researchers. 10,29,58,59 In addition, miR-19 increased the resistance to apoptosis of mouse B-cell lymphoma, 10,29 and chemoresistance of human breast cancer 58 and gastric cancer 59 through directly repressing PTEN expression.…”

“…10 More recent studies have reported that miR-19a or miR-19b-1 promoted the migration and invasion of cervical carcinoma cells, 16 colon cancer cells, 17 and gastric cancer cells through targeting the tumor suppressor MXD1, 14 and Hela, MCF7, and Huh7 cells through targeting TP53. 18 Taken together, these results support that miR-19 is involved in cancer invasion and metastasis; however, the underlying mechanisms remain largely unknown.…”

“…17 In addition, it has been reported that miR-19a/b facilitated the migration, invasion, and metastasis of gastric cancer cells by targeting the tumour suppressor MXD1. 14 miR-19 overexpression induces EMT of lung cancer cells J Li et al Furthermore, Fan et al 18 reported that miR-19b promoted the migration, invasion, and metastasis of Hela, MCF7, and Huh7 cells by targeting TP53. These studies strongly support that miR-19 has a central role in cancer invasion and metastasis by regulating different targets; however, the underlying mechanisms are largely unknown.…”

“…Given that miR-19 is associated with cancer invasion and metastasis and EMT is the central mechanism underlying cancer invasion and metastasis, [10][11][12][13][14][15][16][17][18] the present study aimed to investigate whether miR-19 is able to induce EMT and enhance invasion and metastasis of human cancer cells. Our results showed that enforced expression of miR-19 in lung cancer cells induced EMT, which caused growth inhibition but elevated migration of the cancer cells.…”

The emerging role of miR‐19 in glioma

“…Inhibitory effect of PPARα on glioma cell proliferation is blocked by targeting regulation of miR‐19, progression of tumour is enhanced 37. p53 has also been identified to be the target gene of miR‐19 in Hela cell 40. In glioma, expression of p53 is correlated negatively with that of miR‐19 31.…”