Autophagy regulation by microRNAs: Novel insights into osteosarcoma therapy

Abstract

Osteosarcoma (OS) is a kind of primary bone cancer that is considered as the leading cause of children death. Surgery and chemotherapy are considered as common treatment approaches for OS; the rate of survival for patients is almost 60-70%. Besides the used therapeutic approaches, it seems that there is a crucial need to launch new treatments for OS. In this regard, more understanding about cellular and molecular pathways involved in OS can contribute to recovery and develop new therapeutic platforms. Autophagy is a cellular machinery that digests and degrades dysfunctional proteins and organelles, so it can regulate the cell proliferation and survival. Most of the time, OS cells use autophagy to increase their survival and proliferation and to gain the ability to resist chemotherapy. Although, there are several controversial evidences on how OS cells use autophagy. A variety of cellular and molecular pathways, that is, microRNAs (miRNAs) can modulate autophagy. MiRNAs are some endogenous, approximately 22 nucleotide RNAs that have an important role in posttranscriptional regulation of mRNAs by targeting them. There are many evidences that the various miRNA expressions in OS cells are dysregulated, so it can propel a normal cell to cancerous one by influencing the cell survival, apoptosis, and autophagy, and eventually increased chemoresitance. Hence, miRNAs can be considered as new biomarkers for OS diagnosis, and according to the role of autophagy in OS progression, miRNAs can use inhibiting or promoting autophagy agents. The present review summarizes the effects of

Wnt/β-catenin signaling pathway induces autophagy-mediated temozolomide-resistance in human glioblastoma

“…Autophagy is an evolutionarily conserved cellular catabolic process that has a critical role in maintaining cellular homeostasis through the lysosomal degradation of unnecessary or dysfunctional components during metabolic stress, pathogenic infection, radiation damage, and drug therapy 37 . Since it has been served in both pro-survival and pro-apoptotic mechanisms, the role of autophagy in cancer cell biology is complicated and evolves throughout tumorigenesis 28 , 30 , 38 , 39 . In this study, TMZ-resistant GBM cell lines showed enhanced autophagic processes, such as increased expression of the autophagy-related gene as well as acidic autolysosome formation after TMZ treatment.…”

Targeting aggressive osteosarcoma with a peptidase-enhanced cytotoxic melphalan flufenamide

“…Melflufen could also be combined with other novel approaches to eradicate chemo-resistant osteosarcoma. 50 …”

MicroRNAs and Their Influence on the ZEB Family: Mechanistic Aspects and Therapeutic Applications in Cancer Therapy

“…Non-coding RNAs (ncRNAs) comprise a huge part of human genome and are involved in various molecular pathways and processes [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. They are divided into two characteristic groups: house-keeping and regulatory molecules [ 49 ].…”