MicroRNA‑448 inhibits the progression of retinoblastoma by directly targeting ROCK1 and regulating PI3K/AKT signalling pathway

Abstract

Retinoblastoma (RB) is the most common primary intraocular malignancy during infancy and childhood worldwide. Numerous microRNAs (miRNAs) contribute to RB initiation and progression through the regulation of cell proliferation, cycle, apoptosis, migration, invasion and metastasis. Therefore, further investigation concerning the expression, roles and associated mechanisms of RB‑related miRNAs may be beneficial to develop novel strategies for patients with this malignancy. Recently, miRNA‑448 (miR‑448) has been reported to be aberrantly expressed and to play an important role in several types of human cancer. However, the expression patterns and biological roles of miR‑448 in RB have not been studied. The aim of the present study was to detect the expression levels of miR‑448 and investigate its functions in RB and its associated molecular mechanisms. In the present study, miR‑448 was significantly downregulated in RB tissues and cell lines. Upregulation of miR‑448 decreased cell proliferation and invasion and increased apoptosis in RB cells. Additionally, ρ‑associated coiled‑coil containing protein kinase 1 (ROCK1) was validated as a novel direct target gene of miR‑448 in RB. ROCK1 was overexpressed in RB tissues and inversely correlated with miR‑448 expression. Furthermore, ROCK1 silencing induced effects on the proliferation, invasion and apoptosis of RB cells similar to those observed following miR‑448 overexpression. Moreover, restoration of miR‑448 expression markedly reversed the effects of miR‑448 overexpression on RB cells, further supporting the hypothesis that ROCK1 is a direct functional target of miR‑448 in RB. Importantly, miR‑448 targeted ROCK1 to inhibit the activation of the PI3K/AKT signalling pathway in RB. These results demonstrated that miR‑448 may serve as a tumour suppressor in RB by directly targeting ROCK1 and regulating the PI3K/AKT signalling pathway, thereby suggesting that miR‑448 may be an effective therapeutic target for treating this aggressive cancer.

miR-135a inhibits malignant proliferation and diffusion of non-small cell lung cancer cells by down-regulating ROCK1 protein

“…In addition, miR-135a is abnormally down-regulated in gastric cancer, glioma, endometrial cancer and other tumors, while ROCK1 is also abnormally over-expressed in osteosarcoma, hepatocellular carcinoma, retinoblastoma and other cancers. Reverse regulation of the miR-135a and ROCK1 expressions has anti-cancer effects to varying degrees [22][23][24][25][26][27]. Further analysis of the ability of miR-135a and ROCK1 to differentiate NSCLC revealed that the AUC of both in the diagnosis of NSCLC was no less than 0.85, suggesting that both had a high value in screening NSCLC and might serve as biomarkers for the early diagnosis of NSCLC.…”

Long noncoding RNA DANCR, working as a competitive endogenous RNA, promotes ROCK1-mediated proliferation and metastasis via decoying of miR-335-5p and miR-1972 in osteosarcoma

“…As the first encouraging result, we verified that DANCR did promote osteosarcoma cells’ proliferation and metastasis via up-regulation of ROCK1. According to the previous researches, ROCK1 could be targeted by many miRNAs [ 41 – 44 ]. Also, it is well known that lncRNA can regulate numbers of miRNAs at the same time, and one miRNA can regulate an army of downstream target genes.…”

MicroRNA‑874 prohibits the proliferation and invasion of retinoblastoma cells by directly targeting metadherin

“…Over half of miRNAs are located at cancer-related genomic regions or fragile sites, indicating that miRNAs may be closely related to cancer initiation and progression (10). Numerous miRNAs are deregulated in RB, such as miR-138 (11), miR-448 (12), miR-498 (13) and miR-613 (14). miRNAs deregulation plays critical roles in RB oncogenesis and development by regulating cell proliferation, apoptosis, cycle, metastasis and invasion (15,16).…”