miR-340: A multifunctional role in human malignant diseases

Abstract

MicroRNAs (miRNAs) are a class of short non-coding RNAs of approximately 22 nucleotides in length, which function by binding to the 3' UTR sequences of their target mRNAs. It has been reported that dysregulated miRNAs play pivotal roles in numerous diseases, including cancers, such as gastric, breast, colorectal, ovarian, and other cancers. Recent research efforts have been devoted to translating these basic discoveries into clinical applications that could improve the therapeutic outcome in patients with cancer. Early studies have shown that miR-340 may act either as an oncogene or a tumor suppressor by targeting genes related to proliferation, apoptosis, and metastasis, as well as those associated with diagnosis, treatment, chemoresistance, and prognosis. miR-340 has been shown to have a role in other diseases, such as autoimmune diseases, acute stroke, and alcoholic steatohepatitis. Nevertheless, the roles of miR-340 in human malignancies are still unclear, and the associated mechanisms are complex, involving a variety of signaling pathways, such as Wnt/β-catenin and the JAK-STAT pathways. Herein, we review the crucial roles of miR-340 in human cancers through the analysis of the latest research studies, with the aim of clarifying miR-340 function in malignant disease diagnosis, treatment, and prognosis, and to propose further investigations.

miR-340-5p Mediates Cardiomyocyte Oxidative Stress in Diabetes-Induced Cardiac Dysfunction by Targeting Mcl-1

“…miR-340-5p, which localized in 5q35, has been identified to contribute to participate in the initiation and progression of several diseases. Recently, miR-340-5p has been revealed that participates in the initiation and progression of tumor by targeting multiple oncogenes, such as c-Met, FHL2, ROCK1, and SKP2 [ 11 ]. Importantly, numerous evidences showed that induced miR-340-5p expression promotes cellular apoptosis and suppresses cell viability, thus inhibiting tumor development [ 12 – 14 ].…”

The Potential Role of CDH1 as an Oncogene Combined With Related miRNAs and Their Diagnostic Value in Breast Cancer

“…Among them, miR-20a overexpression was positively linked to the stemness characteristics and poor prognosis of BC, which might be the pro-oncogene associated with stemness progression of breast cancer. In fact, miR-340 has been widely reported as a tumor suppressor ( 49 ). In BC, miR-340 overexpression was shown to significantly inhibit BC cell migration and invasion ( 50 , 51 ).…”

Implication of microRNAs in Carcinogenesis with Emphasis on Hematological Malignancies and Clinical Translation

“…The first miRNA-targeted drug was miravirsen (SPC3649), a locked nucleic acid (LNA)-modified antisense oligonucleotide targeting miR-122, that is currently in phase II clinical trial for the treatment of hepatitis C virus infection [ 190 , 191 ]. MRX34 (miRNA Therapeutics), containing a double-stranded miR-34a mimic encapsulated in ionizable liposomes, was the first miRNA mimic to enter a phase I clinical trial in 2013 (NCT01829971) in several solid tumors and hematological malignancies [ 3 , 192 ]; however, the trial was closed due to severe immune-related adverse events [ 6 ].…”

“…The biogenesis of miRNAs is a multistep process, including the transcription of primary double-stranded transcripts, nuclear processing by the RNase III endonuclease enzyme Drosha, nucleocytoplasmic export by Exportin-5, cytoplasmic cleavage by Dicer, and formation of the RNA-induced silencing complex (RISC) with Argonaute (Ago) proteins [ 4 ]. miRNAs are posttranscriptional regulators of gene expression, that function primarily by binding to the 3′ untranslated regions (3′UTR) of their target messenger RNAs (mRNAs), resulting in the inhibition of translation [ 5 , 6 ]. Depending on the microenvironment, miRNAs can target multiple mRNAs, and a single mRNA can also be targeted by several different miRNAs [ 7 ].…”

“…Depending on the microenvironment, miRNAs can target multiple mRNAs, and a single mRNA can also be targeted by several different miRNAs [ 7 ]. miRNAs are involved in a wide range of biological processes such as hematopoiesis [ 8 ], while dysregulation of miRNA expression levels plays pivotal roles in numerous diseases [ 6 ]. The finding that approximately 50 percent of human miRNAs are located at cancer-associated genomic regions (CAGR) suggests that miRNAs are important puzzle-pieces in the pathogenesis of cancer [ 9 ].…”