MicroRNA-99a/100 promotes apoptosis by targeting mTOR in human esophageal squamous cell carcinoma

Abstract

Recently, microRNA-99 family members, such as miR-99a/b and miR-100, have been reported to exhibit abnormal expression in various malignant tumors, but their functions in carcinomas are controversial. In this study, we focused on miR-99a and miR-100, which were determined to be universally downregulated in esophageal squamous cell carcinoma, and investigated their functions and potential mechanisms of action. The downregulation of miR-99a/100 was validated by qRT-PCR in 101 ESCC surgical tissue samples and in 3 ESCC cell lines. The overexpression of miR-99a and miR-100 via the transient transfection of the corresponding precursor molecules inhibited cell proliferation by inducing apoptosis in the ESCC cell lines. To investigate the molecular mechanism of miR-99a/100-induced apoptosis, luciferase reporter assays and Western blots were performed to demonstrate that the overexpression of miR-99a/100 suppressed the expression of mTOR by directly targeting its 3'UTR in a post-transcriptional manner. Clinically, the decreased expression of miR-99a/100 was associated with worse overall survival in ESCC patients. In conclusion, these results indicated that miR-99a and miR-100 inhibited cell proliferation by suppressing mTOR in ESCC cell lines, and therefore, the miR-99a/100-mTOR signaling pathway is a potential therapeutic target for inducing apoptosis to combat ESCC.

microRNA-186 inhibits cell proliferation and induces apoptosis in human esophageal squamous cell carcinoma by targeting SKP2

“…miRNAs, including miR-21, miR-31, miR-577, etc, act as oncogenes, [19][20][21] while others such as Let-7, miR-98, miR-100, miR-138, miR-143, miR-150, etc, function as tumor suppressors. [22][23][24][25][26][27] However, the role of miR-186 in ESCC progression remains uninvestigated.…”

Multiple Roles of MicroRNA-100 in Human Cancer and its Therapeutic Potential

“…Similarly, mTOR is also involved in the ability of miR-100 ability to suppress cell proliferation and colony formation in bladder cancer [50]. It was demonstrated by Sun et al that miR-100 was significantly decreased in ESCC and the tumor suppressor function of miR-100 resulted from inhibiting tumor cell growth and inducing apoptosis by targeting mTOR [27]. As an mTOR inhibitor, the rapamycin analog RAD001 has recently been shown to decrease tumor growth in a xenograft model of clear cell ovarian cancer [95].…”

Neuroprotective effect of microRNA-99a against focal cerebral ischemia–reperfusion injury in mice

“…MiR-99a has been proved to suppress tumorigenicity [12][13][14][15][16][17][18], and mTOR pathway has been linked to miR-99a-induced G1 arrest [16][17][18]. In addition, miR-99a exerts pro-apoptotic and anti-apoptotic effects respectively in tumor cells and ischemic cardiomyocytes [19,20]. However, the clinical significance and function of miR-99a in ischemic stroke and neural cell cycle activation are unknown.…”