The Role of Non-Coding RNAs in Autophagy During Carcinogenesis

Abstract

Macroautophagy (autophagy herein) is a cellular stress response and a survival pathway involved in self-renewal and quality control processes to maintain cellular homeostasis. The alteration of autophagy has been implicated in numerous diseases such as cancer where it plays a dual role. Autophagy serves as a tumor suppressor in the early phases of cancer formation with the restoration of homeostasis and eliminating cellular altered constituents, yet in later phases, autophagy may support and/or facilitate tumor growth, metastasis and may contribute to treatment resistance. Key components of autophagy interact with either pro- and anti-apoptotic factors regulating the proximity of tumor cells to apoptotic cliff promoting cell survival. Autophagy is regulated by key cell signaling pathways such as Akt (protein kinase B, PKB), mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) involved in cell survival and metabolism. The expression of critical members of upstream cell signaling, as well as those directly involved in the autophagic and apoptotic machineries are regulated by microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Consequently, non-coding RNAs play a relevant role in carcinogenesis and treatment response in cancer. The review is an update of the current knowledge in the regulation by miRNA and lncRNA of the autophagic components and their functional impact to provide an integrated and comprehensive regulatory network of autophagy in cancer.

Role of autophagy and its regulation by noncoding RNAs in ovarian cancer

“…It should be noted that the expression of ATGs and autophagy-related signaling pathways is modulated by noncoding RNAs (ncRNAs) at various levels, from transcriptional regulation to posttranslational protein modification. 8,9 A growing body of evidence indicates that ncRNA-mediated autophagy is associated with malignant behaviors such as proliferation, metastasis, and chemoresistance in OC. [10][11][12] The clarification of the regulatory roles of ncRNAs on autophagy in OC could provide promising therapeutic strategies for this disease.…”

“…97 MiRNAs are a kind of single-stranded molecules with a length of 19-25 nucleotides, and they can suppress mRNA translation or trigger their degradation by pairing with the complementary sequences at the 3′-UTR of mRNAs of target genes, thus controlling the expression of genes. 9 MiRNAs have dual functions in tumorigenesis: serving as tumor suppressors by blocking the translation of mRNA of target genes that induce malignant transformation; conversely, playing oncogenic role via initiating the degradation of mRNA of tumor suppressor genes. 97 LncRNAs are a class of transcripts of over 200 nucleotides and regulate gene expression through three well-characterized action mechanisms, including interacting with DNA or chromatin-modifying enzymes to influence genetic transcription, sponging miR-NAs or binding to mRNAs to affect translation, and acting as scaffolds of proteins to block their functions.…”

Focusing on the Role of Natural Products in Overcoming Cancer Drug Resistance: An Autophagy-Based Perspective

“…The most well-known class IIb deacetylase, histone deacetylase 6 (HDAC6), has been demonstrated to impede autophagy by deacetylating TFEB and FOXO1, two key players in the process [ 23 ]. Additionally, non-coding RNAs including circRNAs, lncRNAs, and microRNAs play a role in autophagy initiation and inhibition [ 24 , 25 ]. Moreover, autophagy and apoptotic signaling are interdependent and interact with each other.…”

Curcumin Targeting Non-Coding RNAs in Colorectal Cancer: Therapeutic and Biomarker Implications

“…In the early stage of tumorigenesis, autophagy can act as a tumor suppressor, which restores homeostasis and eliminates cancerous cell components. However, in the advanced stage of tumors, autophagy may promote tumor growth and metastasis, which may produce therapeutic resistance [ 54 ]. Compared with normal tissues, the abnormal expression of miRNAs in cancer tissues is mainly manifested as the downregulation or deletion of miRNAs with tumor-suppressor functions and the overexpression of miRNAs with oncogenic functions [ 55 ].…”