The Emerging Role of MicroRNAs and Autophagy Mechanism in Pancreatic Cancer Progression: Future Therapeutic Approaches

Abstract

Pancreatic cancer constitutes the fourth most frequent cause of death due to malignancy in the US. Despite the new therapeutic modalities, the management of pancreatic ductal adenocarcinoma (PDAC) is considered a difficult task for clinicians due to the fact that is usually diagnosed in already advanced stages and it is relatively resistant to the current chemotherapeutic agents. The molecular background analysis of pancreatic malignant tumors, which includes various epigenetic and genetic alterations, opens new horizons for the development of novel diagnostic and therapeutic strategies. The interplay between miRNAs, autophagy pathway, and pancreatic carcinogenesis is in the spotlight of the current research. There is strong evidence that miRNAs take part in carcinogenesis either as tumor inhibitors that combat the oncogene expression or as promoters (oncomiRs) by acting as oncogenes by interfering with various cell functions such as proliferation, programmed cell death, and metabolic and signaling pathways. Deregulation of the expression levels of various miRNAs is closely associated with tumor growth, progression, and dissemination, as well as low sensitivity to chemotherapeutic agents. Similarly, autophagy despite constituting a pivotal homeostatic mechanism for cell survival has a binary role in PDAC, either as an inhibitor or promoter of carcinogenesis. The emerging role of miRNAs in autophagy gets a great deal of attention as it opens new opportunities for the development of novel therapeutic strategies for the management of this aggressive and chemoresistant malignancy. In this review, we will shed light on the interplay between miRNAs and the autophagy mechanism for pancreatic cancer development and progression.

A Current Synopsis of the Emerging Role of Extracellular Vesicles and Micro-RNAs in Pancreatic Cancer: A Forward-Looking Plan for Diagnosis and Treatment

“…Deep knowledge of the miRNA tumor profiles including PDAC, could lead to the development of powerful anti-cancer therapeutic tools. There are several alterations in the expression levels of miRNAs in PDAC, which can facilitate its diagnosis, and can be utilized as targets for tumor suppression via inhibiting the oncomiRs or enhancing the expression of tumor-suppressive miRNAs [ 35 ].…”

“…Moreover, MALAT1 induces activation of the autophagy pathway. PDAC constitutes a malignancy that presents overregulation of autophagy that needs to be suppressed, compared to other malignancies, in which autophagy inhibition could lead to oncogenesis [ 35 , 73 , 75 , 76 ]. Furthermore, AFAP1-AS1 promotes PDAC growth and invasion by upregulating the IGF1R oncogene via miR-133a sequestration, which regulates its translation [ 77 ].…”

The emerging roles of miRNA-mediated autophagy in ovarian cancer

“…However, recent studies have demonstrated evidence of mutual control between the autophagy pathway and the miRNA machinery. Indeed, in some other cases, degradation mediated through autophagy and autophagy can target miRNA and miRNA machinery components thus playing an important role in the control of cancer progression [61][62][63].…”

Editorial on “Exosome-mediated transfer of circRNA563 promoting hepatocellular carcinoma by targeting the microRNA148a-3p/metal-regulatory transcription factor-1 pathway”

“…There is a call for the discovery and development of novel therapeutic approaches, with the understanding of the molecular complexity of this malignancy being pivotal. The role of extracellular vesicles (EVs) and non-coding RNA molecules and their implications in HCC development and progression are in the spotlight of their ongoing studies, aiming to discover novel therapeutic targets and strategies[ 3 ].…”