ABSTRACT
The current study aimed to evaluate the expression and role of miR-212 in the progression of pituitary adenoma (PA), thereby providing a theoretical basis and potential therapy methods for PA patients. Our data showed that miR-212 levels were significantly reduced in PA tissues than normal pituitary tissues. However, no significant difference was identified in the serum of PA patients and healthy control. In addition, the expression of miR-212 in invasive PA was significantly lower than that in noninvasive and normal pituitary tissues. Moreover, the level of miR-212 was decreased with the increase of tumor invasion. Meanwhile, the expression of miR-212 in giant adenomas was significantly lower than that in macroadenomas and microadenomas. Furthermore, inhibition of miR-212 significantly enhanced the proliferation and invasive capacity of GH3 cells. Dual luciferase reporter assay and western blot analysis confirmed that c-Met was a target gene of miR-212. More importantly, upregulation of c-Met significantly prompted PA cell proliferation mainly as a result of the enhanced level of phosphorylation of AKT. This effect could be abolished when c-Met was silenced in GH3 cells. In summary, reduced miR-212 expression in PA contributed to abnormal cancer cell proliferation and invasion mainly by targeting c-Met.
Subject(s)
Pituitary Neoplasms/metabolism , Proto-Oncogene Proteins c-met/metabolism , 3' Untranslated Regions/genetics , 3' Untranslated Regions/physiology , Animals , Apoptosis/genetics , Apoptosis/physiology , Blotting, Western , Cell Line , Cell Proliferation/genetics , Cell Proliferation/physiology , Female , Gene Expression Regulation, Neoplastic/genetics , Humans , Male , Middle Aged , Pituitary Neoplasms/pathology , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-met/genetics , Rats , Real-Time Polymerase Chain ReactionABSTRACT
BACKGROUND: Alzheimer-associated neuronal thread protein (AD7c-NTP) has been reported to have high diagnostic accuracy in patients with Alzheimer's disease (AD). OBJECTIVE: To determine the diagnostic accuracy of urinary AD7c-NTP for the diagnosis of AD in patients with suspected AD. METHODS: We searched MEDLINE (January 1950 to date) and other electronic databases (from inception to date) for diagnostic accuracy studies that compared urinary AD7c-NTP to the standard clinical diagnosis of AD. We conducted citation searches and screened the reference lists of included studies. Studies were assessed for methodological quality using QUADAS. Summary receiver operating characteristic curves were used to summarize overall test performance. RESULT: Nine studies met our inclusion criteria. The summary estimates of the urinary AD7c-NTP assay for probable or possible AD were as follows: SEN, 0.87 (95%CI: 0.80-0.91); SPE, 0.89 (95%CI: 0.87-0.91); PLR, 8.13 (95% CI: 6.60-10.02); and NLR, 0.15 (95% CI: 0.10-0.22). The four summary estimates of urinary AD7c-NTP assay for probable AD were 0.89 (95% CI: 0.86-0.92), 0.90 (95% CI: 0.88-0.92), 8.88 (95% CI: 7.09-11.12), and 0.12 (95% CI: 0.09-0.16), with no obvious heterogeneity. CONCLUSION: Urinary AD7c-NTP is a sensitive and specific test for the diagnosis of probable AD. However, whether urinary AD7c-NTP can be used as an early marker is still unknown.