miR-374a-5p: A New Target for Diagnosis and Drug Resistance Therapy in Gastric Cancer

Abstract

Chemoresistance is one of the causes associated with poor prognosis in gastric cancer. MicroRNAs (miRNAs) are important regulators of chemoresistance. Exosome-mediated delivery of anti-cancer molecules and drugs have emerged as a new approach for cancer therapy. We first examined the expression of miR-374a-5p in gastric cancer serum by qRT-PCR and explored the clinicopathological parameters. We then performed in vitro cell and molecular studies, including CCK-8 assay, flow cytometry, qRT-PCR, and western blot, to determine the roles of miR-374a-5p in gastric cancer chemoresistance and identified its downstream target by luciferase reporter assay. We also used in vivo animal studies to evaluate the therapeutic efficacy of miR-374a-5p inhibitor and exosome-mediated delivery of miR-374a-5p inhibitor in gastric cancer. miR-374a-5p expression level was elevated in gastric cancer serum, and its upregulation predicted poor prognosis. miR-374a-5p overexpression promoted while miR-374a-5p knockdown inhibited gastric cancer chemoresistance in vitro and in vivo. miR-374a-5p bound to Neurod1 to antagonize its effect on chemoresistance. Exosome-mediated delivery of miR-374a-5p inhibitor could increase Neurod1 expression, promote cell apoptosis, and suppress chemoresistance. miR-374a-5p had a promoting role in gastric cancer chemoresistance, which would provide a novel biomarker for gastric cancer diagnosis and prognosis and offer a potential target for gastric cancer drug resistance therapy.

RNA-Seq Profiling of Serum Exosomal Circular RNAs Reveals Circ-PNN as a Potential Biomarker for Human Colorectal Cancer

“…The reactions were incubated at 37 • C, 30 min, followed by 85 • C for 5 s. The relative gene expression of RNA was determined using the CFX96 Real-Time PCR Detection System (Bio-Rad Laboratories, Hercules, CA, USA) as follows: 95 • C for 30 s, followed by 40 cycles at 95 • C for 5 s, and a pre-selected annealing temperature 60 • C for 30 s was used as the PCR condition. Based on previous literature, the housekeeping gene β-actin was used to normalize the relative expression levels of circRNA and linear mRNA (43,44), whereas U6 was utilized as the internal reference of miRNA (45,46). The relative expressions of serum exosomal circRNAs were calculated by the comparative 2 − Ct method as follows: Ct = Ct target gene -Ct internal reference, and Ct = Ct experimental group − Ct control group (47).…”

Function and mechanisms of microRNA‑20a in colorectal cancer (Review)

“…The early detection and treatment of CRC is important for controlling the progression of the disease. A number of studies have demonstrated that miRNA can be used as a biomarker for the diagnosis and prognosis of CRC, and this can provide information on tumor initiation, development, invasion, metastasis and response to chemotherapy (16,39,111,112,122,123). A number of studies have also confirmed that miR-20a is significantly upregulated and serves an important role in the development, progression and therapeutic response of CRC, and it can be used as a biomarker for CRC in tissues, serum and fecal samples (124).…”

Evaluation of plasma exosomal microRNAs as circulating biomarkers for progression and metastasis of gastric cancer

“…Dear Editor, Till now, abundant studies have shown that exosomal miRNA may have potential clinical application value as biomarkers for diagnosis and evaluation in gastric cancer (GC). 1,2 However, current researches not only rarely refer to plasma exosomal miRNAs (PEMs) for progression and metastasis prediction, but also seem to be limited to individual PEM identification, ignoring that miRNAs are often expressed in clusters to achieve regulatory functions. Thus inspiring us to conduct this systemic and comprehensive studies on PEMs to excavate their value in accurate evaluation of progression and metastasis in GC.…”