MicroRNA-492 overexpression exerts suppressive effects on the progression of osteosarcoma by targeting PAK7

Abstract

MicroRNAs (miRNAs or miRs), which are a class of non-coding RNAs, have emerged as effective modulators of various aspects of biological processes. Accumulating evidence has established significant associations between the dysregulation of miRs and tumorigenesis in various types of cancer. However, the role of miR‑492, particularly in osteosarcoma (OS) remains elusive. In present study, we demonstrated that miR‑492 functions as putative tumor suppressor miR in OS. The level of miR‑492 was frequently downregulated in both OS tissues and cell lines. Moreover, the ectopic overexpression of miR‑492 effectively inhibited the proliferation, migration and invasion of OS cell lines. Furthermore, transfection with a miR‑492 overexpression vector also strongly attenuated the growth of xenograft tumors in vivo. p21-activated kinase (PAK7) was identified as the putative target of miR‑492 in OS, and we further found a significantly inverse correlation between PAK7 and miR‑492 in OS specimens. Taken together, our study has unraveled a novel role for miR‑492 in OS and may help in establishing the rationale for more effective treatment strategies for OS via miR regulation.

Inhibition of microRNA‑492 attenuates cell proliferation and invasion in retinoblastoma via directly targeting LATS2

“…miR-492 downregulation is significantly correlated with the pelvic lymph node metastasis of patients with cervical cancer (20). Weakly expressed miR-492 has also been observed in osteosarcoma (21) and clear cell renal cell carcinoma (22). By contrast, miR-492 is highly expressed in hepatoblastoma tissues and cell lines.…”

“…miR-492 upregulation inhibits the proliferation and invasion of cervical cancer cells, and increases the sensitivity of cells to irradiation by inducing apoptosis (20). In osteosarcoma, the resumption of miR-492 expression suppresses cell growth and metastasis in vitro, and decreases in vivo tumour growth (21). In clear cell renal cell carcinoma, miR-492 restoration restricts cell proliferation and invasion, induces cell apoptosis and promotes cell adhesion (22).…”

“…Researchers have identified numerous target genes of miR-492, including TIMP2 (20) in cervical cancer, PAK7 (21) in osteosarcoma, CD44 (26) in hepatoblastoma, SOX7 (24) in breast cancer and PTEN (23) in hepatic cancer. LATS2, which is a member of the serine/threonine AGC kinase family, was validated as a direct target of miR-492 in RB.…”

“…Therefore, miRNAs may serve as potential diagnostic biomarkers and therapeutic targets for patients with RB. miR-492 is reportedly downregulated in cervical cancer (20), osteosarcoma (21) and clear cell renal cell carcinoma (22). By contrast, miR-492 is upregulated in hepatoblastoma, hepatic cancer (23) and breast cancer (24).…”

Inhibiting p21-activated kinase (PAK7) enhances radiosensitivity in hepatocellular carcinoma

“…Previous research has shown that SOX21-AS1/miR-144-3p/PAK7 axis acts as a carcinogen in the development of glioma through regulating its cell proliferation. 23 Notably, PAK7 overexpression was also correlated with the abnormal proliferation of various tumor cells, such as osteosarcoma 32 and gastric cancer. 33 It should be noted that the ectopic introduction of miR-526a into HCC cells resulted in a significant decrease in cell apoptosis via targeting PAK7 according to the work of Zhan et al 18 In our work, PAK7 shRNA was able to induce the IR-caused decrease in the viability of HCC cells, while reduce the clone formation ability of HCC cells.…”