MicroRNA-92a promotes cell viability and invasion in cervical cancer via directly targeting Dickkopf-related protein 3

Abstract

Abstract. was recently reported to have an oncogenic role in cervical cancer; however, the underlying mechanism remains largely unclear. The present study aimed to investigate the expression, clinical significance and regulatory mechanism of miR-92a in cervical cancer. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) data indicated that miR-92a was significantly upregulated in cervical cancer tissues compared with matched adjacent non-tumor tissues (P<0.01). High expression of miR-92a was significantly associated with poor differentiation (P=0.031), advanced clinical stage (P=0.011) and lymph node metastasis (P=0.014), but not associated with age, tumor size and distant metastasis. Knockdown of miR-92a significantly inhibited the viability and invasion of cervical cancer HeLa cells, while overexpression of miR-92a significantly enhanced HeLa cell viability and invasion (P<0.01). Luciferase reporter assay identified Dickkopf-related protein 3 (DKK3) as a target gene of miR-92a, and the protein expression of DKK3 was negatively regulated by miR-92a in HeLa cells. Furthermore, overexpression of DKK3 significantly eliminated the stimulative effects of miR-92a on HeLa cell viability and invasion (P<0.01). Additionally, DKK3 was significantly downregulated in cervical cancer tissues compared with adjacent non-tumor tissues (P<0.01), inversely correlated to the miR-92a levels in cervical cancer tissues (P<0.01). In summary, the present study indicated that miR-92a promotes cell viability and invasion in cervical cancer, partly at least, via inhibiting the protein expression of DKK3. Therefore, the present study highlights the clinical significance of the miR-92a/DKK3 axis in cervical cancer.

EGF-mediated reduced miR-92a-1-5p controls HTR-8/SVneo cell invasion through activation of MAPK8 and FAS which in turn increase MMP-2/-9 expression

“…1 ). Role of increased expression of miR-92a-1-5p is observed in cervical cancer cells, and is believed to promote cell viability and invasion 14 . As opposed to the observed increased miR-92a-1-5p expression in cervical cancer cells, inhibition of miR-92a-1-5p was observed in HTR-8/SVneo trophoblast cells during increased invasion.…”

“…The miR-92a-1-5p (previously known as miR-92a-1*) is the least described among the two. Whereas, miR-92a (now known as miR-92a-3p) is reported to be overexpressed in various types of tumors, and increases cell proliferation and invasion 12 – 14 .…”

MicroRNA‐92a inhibits macrophage antiviral response by targeting retinoic acid inducible gene‐I

“…MiR‐92a was first identified as one component of a miR17‐92 cluster within a 15S sediment particle in HeLa cell lysate . A number of studies have demonstrated the abnormal expression and regulatory roles of miR‐92a in patients with many types of cancer . In most cases, miR‐92a functions as a tumor promoter through promoting tumor proliferation, suppressing tumor apoptosis and enhancing tumor invasion and metastasis.…”

“…miR‐92a, a member of the miR‐17‐92 cluster, is reportedly abnormally expressed in many types of cancer, including leukemia, hepatocellular cancer and esophageal squamous cell carcinoma . During these cancerous diseases, the roles of miR‐92a mainly involve regulating cell proliferation, migration and invasion.…”

Dickkopf homolog 3 (DKK3): A candidate for detection and treatment of cancers?

“…Indeed, the latter has been identified as a target gene of miR‐92a in HeLa cells. Specifically, Luo et al () showed that miR‐92a promotes cell viability and invasion in cervical cancer, via inhibiting the protein expression of DKK3.…”