Crosstalk between noncoding RNAs and ferroptosis: new dawn for overcoming cancer progression

Abstract

Cancer progression including proliferation, metastasis, and chemoresistance has become a serious hindrance to cancer therapy. This phenomenon mainly derives from the innate insensitive or acquired resistance of cancer cells to apoptosis. Ferroptosis is a newly discovered mechanism of programmed cell death characterized by peroxidation of the lipid membrane induced by reactive oxygen species. Ferroptosis has been confirmed to eliminate cancer cells in an apoptosis-independent manner, however, the specific regulatory mechanism of ferroptosis is still unknown. The use of ferroptosis for overcoming cancer progression is limited. Noncoding RNAs have been found to play an important roles in cancer. They regulate gene expression to affect biological processes of cancer cells such as proliferation, cell cycle, and cell death. Thus far, the functions of ncRNAs in ferroptosis of cancer cells have been examined, and the specific mechanisms by which noncoding RNAs regulate ferroptosis have been partially discovered. However, there is no summary of ferroptosis associated noncoding RNAs and their functions in different cancer types. In this review, we discuss the roles of ferroptosis-associated noncoding RNAs in detail. Moreover, future work regarding the interaction between noncoding RNAs and ferroptosis is proposed, the possible obstacles are predicted and associated solutions are put forward. This review will deepen our understanding of the relationship between noncoding RNAs and ferroptosis, and provide new insights in targeting noncoding RNAs in ferroptosis associated therapeutic strategies.

Ferroptosis and Cancer: Complex Relationship and Potential Application of Exosomes

“…For instance, miR-18a and miR-218 downregulate GSH levels in hepatocellular carcinoma and bladder cancer separately by targeting GCL ( Anderton et al, 2017 ; Li P. et al, 2017 ), while miR-152 and miR-155 decrease GSH levels in hepatocellular carcinoma and lung cancer separately by targeting GST ( Huang et al, 2010 ; Lv et al, 2016 ), the general pathway by which miRNAs modulate GSH level. GST can be targeted and modulated by various miRNAs, including miR-92b-3p, miR-124, miR129-5P, miR-130b, miR-133a/b, miR-144, miR-153-1/2, miR-186, miR-302c-5p, miR-513a-3p, miR-590-3p/5p, miR-36645p, miR-3714, and let-7a-5p ( Zhang et al, 2020e ). In the meantime, iron metabolism mainly includes the interaction between transferrin (TF) and TF receptor (TFR), which can also be regulated by miRNAs.…”

“…In the meantime, iron metabolism mainly includes the interaction between transferrin (TF) and TF receptor (TFR), which can also be regulated by miRNAs. For example, in CRC and hepatocellular cancer, TFR can be targeted by miRNAs including miR-22, miR-31, miR-141, miR-145, miR-152, miR-182, miR-200a, miR-320, miR-758, and miR19463–65, resulting in a disruption between TF and TFR and the following iron importing process ( Zhang et al, 2020e ). Moreover, iron can regulate miRNA levels.…”

“…Moreover, iron can regulate miRNA levels. Levels of miR-107 and miR-125b can be suppressed by iron in hepatocellular carcinoma ( Lobello et al, 2016 ; Zou et al, 2016 ), while levels of miR-146a and miR-150 can be increased by iron ( Sriramoju et al, 2015 ; Lobello et al, 2016 ), which might be due to iron’s induction of excess ROS ( Zhang et al, 2020e ). Moreover, miRNAs regulate the NRF2 pathway through by targeting Kelch-like ECh-Associated Protein 1 (KEAP1) and NRF2 mRNAs ( Zhang et al, 2020e ).…”

“…Other studies have shown that lncRNAs are associated with iron metabolism and that silencing lncRNA PVT1 suppresses TFR expression and obstructs iron intake via miR-150 ( Xu et al, 2018 ). Evidence also shows that lncRNAs affect the expression of NRF2 by directly and indirectly modulating KEAP1 levels, while NRF2 is associated with lncRNA regulation ( Zhang et al, 2020e ). Besides the above factors, ROS levels can be regulated by lncRNAs.…”

Multi-omics Analysis of Ferroptosis Regulation Patterns and Characterization of Tumor Microenvironment in Patients with Oral Squamous Cell Carcinoma

“…However, other inducers of ferroptosis, such as RLS3, ML162, and ML210, which directly inhibit GPX4 leading to ferroptosis, did not exhibit drug sensitivity in FPscore subtypes. These findings are likely explained by low GPX4 expression in the high FPscore subtype [5,56]. We used CMap to identify other inhibitors that may have antitumor efficacy in OSCC (Figure 6G).…”