Study On Urinary Detection Of MALAT-1to Predict Diagnosis Of Prostate Cancer And Effects Of MALAT-1Silencing On Prostate Caner Cells

[Objective]Metastasis associated in lung adenocarcinoma transcript1(MALAT-1) is found tobe overexpressed in a number of malignancies, including prostate cancer. Tounderstand its role on prostate cancer, we evaluated the expression of MALAT-1inprostate cancer tissues and cell lines and studied the therapeutic effects of MALAT-1silencing on androgen-independent prostate cancer cells in vitro. Due to the limitedspecificity of PSA test, men with elevated PSA levels and negative biopsy results needrepeated biopsy. Thus, we need a more specific diagnostic biomarker. In this study wesought to examine the possible use of MALAT-1as a diagnostic marker for prostatecancer detection in urine.[Materials and methods]Quantitative RT-PCR was used to detect the expression of MALAT-1in prostatecancer tissues and cell lines. Small interference RNA (siRNA) against MALAT-1wasdesigned and the silencing effect was examined by quantitative RT-PCR. Thebiological effects of MALAT-1-siRNA on cells were investigated by examining thecell proliferation by MTT assay and cell colony assay, cell migration by in vitroscratch assay, cell invasion potencies by transwell invasion assay, cell cycle by flowcytometric assay and apoptosis by TUNEL assay.Otherwise,a total of150patients scheduled for prostate biopsy due to elevatedPSA levels(PSA>4.0ng/ml) was registered in this study, including59positive patientsand91negative patients. Post-DRE urine samples were collected and treatedimmediately. Total RNA of urine sediments was extracted using TRIzol reagent. DD3,MALAT-1and PSA levels were determined by Quantitative RT-PCR. Relative DD3and MALAT-1levels were calculated by normalizing DD3and MALAT-1levels tothat of PSA for each sample. We investigated the potential diagnostic efficacy ofMALAT-1alone and the combination of MALAT-1with DD3in Post-DRE urinesamples.[Results]MALAT-1was up-regulated in human prostate cancer tissues and cell lines.Downregulation of MALAT-1by siRNA inhibited the growth, invasion and migrationof prostate cancer cells, induced apoptosis and cell cycle arrest in G0/G1phases inboth androgen-independent prostate cancer cells. MALAT-1is overexpressed inprostate cancer tissues compared with adjacent normal tissues. Relative MALAT-1level is predictive of prostate cancer when used alone（P=0.0016）, which is comparable to relative DD3level. The area under ROC curvewas0.643and0.661for MALAT-1and DD3respectively. Combining MALAT-1andDD3improved the area under ROC curve to0.688.[Conclusions]This study indicates that MALAT-1may be necessary to maintain prostatetumorigenicity and is involved in prostate cancer progression. Thus, MALAT-1mayserve as a potential therapeutic target for androgen-independent prostate cancer. Thequantification of MALAT-1transcripts normalized to PSA transcripts in urinesediments after digital rectal examination is predictive of prostate cancer, whichshows promise as a noninvasive diagnostic tool for prostate early detection.