Strand-specific miR-28-3p and miR-28-5p have differential effects on nasopharyngeal cancer cells proliferation, apoptosis, migration and invasion

Abstract

Background MicroRNAs (miRNAs) play crucial roles in varieties of cancers, particularly in tumorigenesis, progression, and migration. Dysregulation of miR-28 was reported to occur in various types of human malignancies. In humans, two different mature miRNA sequences are excised from opposite arms of the stem-loop pre-miR-28, hsa-miR-28-3p and hsamiR-28-5p. However, the expression and distinct role of miR-28-3p and miR-28-5p in nasopharyngeal carcinoma (NPC) remain undetermined. Methods The expressions of miR-28-3p/-5p in human NPC tissues were tested by quantitative real-time PCR. miR-28-3p/-5p were overexpressed by mimics and silenced by inhibitors. The roles of miR-28-3p/-5p in NPC development were studied using cultured HONE-1 cells. Results The mRNA expression levels of miR-28-3p and -5p were significantly decreased in NPC tissues in comparison with adjacent normal tissues. Overexpression of miR-28-5p suppressed NPC cell proliferation and induced cell cycle arrest and apoptosis, while miR-28-3p promoted NPC cell migration and invasion. The miRNAs effected on different signal pathways: miR-28-5p altered expression of cyclin D1 and influenced the PI3K/AKT signaling pathway. In contrast, miR-28-3p downregulated Nm23-H1 and accelerated the process of EMT. Conclusion miR-28-3p and -5p were both downregulated in NPC tissues but had distinct biological effects in NPC cells. They may serve as potential prognostic markers and therapeutic targets for NPC.

Differences between Well-Differentiated Neuroendocrine Tumors and Ductal Adenocarcinomas of the Pancreas Assessed by Multi-Omics Profiling

“…miR-652 is a critical regulator of proliferation and metastasis in endometrial cancer [65] and functions as an oncogene in gastric cancer [66], melanoma [67], and non-small cell lung cancer (NSCLC) [68]. Overexpression of miR-155-5p characterizes most solid and hematological malignancies [69,70], and dysregulation of miR-28 has been demonstrated in various types of human malignancies [71][72][73]. miR-95 has been shown to act as an oncogene in HCC [74] and NSCLC [75] and as a potential tumor suppressor in osteosarcoma [76].…”

miR‑28‑5p inhibits the migration of breast�cancer by regulating WSB2

“…The overexpression of miR-28-5p in HcT116, RKO and SW480 cells has been shown to reduce cell migration and invasion (10). In addition, miR-28-5p overexpression has been shown to suppress nasopharyngeal cancer cell proliferation and induce cell cycle arrest and apoptosis (11). In the present study, bioinformatics analysis using the Human MicroRNA Expression database (HMEd) also revealed that miR-28-5p was expressed at a low level in breast cancer.…”

“…miR-28-5p directly binds to the LPP mRNA and suppresses its expression, which subsequently inhibits cell migration and adhesion (7). miR-28-5p has been found to function as a tumor suppressor, as it has been shown to be downregulated in various types of human malignancies, such as hepatocellular carcinoma (8), renal cancer (9), colorectal cancer (10) and in nasopharyngeal cancer cells (11). miR-28-5p is involved in the regulation of cell proliferation, apoptosis and metastasis.…”

MiRNAs in Radiotherapy Resistance of Nasopharyngeal Carcinoma

“…The reasons at the gene level include the following two types: the decrease of apoptotic genes or the increase of the expression of anti-apoptotic genes and proliferating genes, and the enhancement of genes related to DNA damage repair, or the expression of cell cycle regulatory genes is dysregulated [6,7,17,18]. Many studies have shown that miRNAs participate in tumor radiation resistance through the above mechanisms [19][20][21].…”