MicroRNA-185 suppresses pancreatic cell proliferation by targeting transcriptional coactivator with PDZ‑binding motif in pancreatic cancer

Abstract

The aim of the present study was to compare the expression of transcriptional coactivator with the PDZ-binding motif (TAZ) in pancreatic cancer (PC) patients, and to investigate the regulation mechanisms of TAZ in the proliferation of PC. PC tissues and matched peritumoral tissues, pancreatic juice and serum were collected from PC patients who underwent pancreatectomy between June 2012 and December 2015 at the Affiliated Hospital of Qingdao University (Qingdao, China). Pancreatic juice and serum were collected from patients with chronic pancreatitis as a control. The levels of taz mRNA expression in the samples were examined by reverse-transcription quantitative polymerase chain reaction, and the protein expression of TAZ was assessed by western blot analysis and ELISA. MicroRNAs (miRNAs) that regulate TAZ expression were also predicted by bioinformatics analysis and validated by dual luciferase reporter and rescue assays. In addition, the proliferation of PC cells was evaluated after transfection with TAZ small interfering RNA (siRNA) or its upstream miRNA agomir. Expression of TAZ was significantly increased in the PC tissues, pancreatic juice and serum of PC patients at the mRNA and protein levels compared with controls (P<0.05). Furthermore, TAZ was predicted and verified to be a target of miRNA (miR)-185, and miR-185 and TAZ were inversely expressed in samples from PC patients (P<0.05). In addition, TAZ siRNA or agomiR-185 transfection significantly inhibited human pancreatic adenocarcinoma cell proliferation (P<0.05). However, overexpression of TAZ in the agomiR-185 group rescued the inhibition (P<0.05). Finally, the expression of TAZ effector proteins, namely ankyrin repeat domain-containing protein and cysteine-rich 61, were upregulated in PC tissues (P<0.05), but repressed following transfection of PC cells with agomiR-185 (P<0.05). Thus, miR-185 may regulate the proliferation of PC by targeting TAZ, making it a promising diagnostic marker for PC.

Identification of Spindle and Kinetochore-Associated Family Genes as Therapeutic Targets and Prognostic Biomarkers in Pancreas Ductal Adenocarcinoma Microenvironment

“…The miRNAs identified in our study have been associated with deteriorated neoplastic malignant phenotype such as proliferation, cell cycle, invasion, drug resistance, and angiogenesis (94)(95)(96)(97)(98). In fact, miR-185, miR-96, miR-218, miR-137, and miR-338 have been proven to exhibit therapeutic and prognostic value in PDAC, indicating that the SKA gene may be one of the target genes for these miRNAs (99)(100)(101)(102)(103).…”

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

“…For YAP, the only upstream regulatory transcription factor reported so far is cyclic adenosine monophosphate response element-binding protein (CREB) [46]. In cancer, both YAP and TAZ RNA are frequently increased, but the mechanisms behind this upregulation remain largely elusive and may involve both transcriptional and posttranscriptional mechanisms through suppression of the YAP/TAZ regulatory microRNAs, including miR-15a, miR-141-3p, mir -194, miR-195, miR-375, miR-381, miR-584, miR-125, miR-185, miR-9-3p and miR-129-5p, to name a few [47][48][49][50][51][52][53][54][55][56][57].…”

miR‑212 regulated by HIF‑1α promotes the progression of pancreatic cancer

“…Accumulating evidence reveals that miRNA dysfunction influences the metastasis, chemo-radioresistance and overall survival time of patients with cancer, including patients with PDAC (7)(8)(9)(10). Previous reports have revealed miRNA involvement in PDAC progression, including roles of miR-216b (11), miR-10a-5p (10), miR-374b-5p (12), miR-1271 (13), miR-7-5p (14), miR-4295 (15) and miR-185 (16). However, the molecular mechanisms underlying the involvement of miRNAs in PDAC progression remain unclear.…”