The endocannabinoid system, a new gatekeeper in the pharmacology of human hepatocellular carcinoma.

Despite numerous prevention methodologies and treatment options, hepatocellular carcinoma (HCC) still remains as the third leading life-threatening cancer. It is thus pertinent to develop new treatment modality to fight this devastating carcinoma. Ample recent studies have shown the anti-inflammatory and antitumor roles of the endocannabinoid system in various forms of cancers. Preclinical studies have also confirmed that cannabinoid therapy can be an optimal regimen for cancer treatments. The endocannabinoid system is involved in many cancer-related processes, including induction of endoplasmic reticulum (ER) stress-dependent apoptosis, autophagy, PITRK and ERK signaling pathways, cell invasion, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) phenotypes. Moreover, changes in signaling transduction of the endocannabinoid system can be a potential diagnostic and prognostic biomarker for HCC. Due to its pivotal role in lipid metabolism, the endocannabinoid system affects metabolic reprogramming as well as lipid content of exosomes. In addition, due to the importance of non-coding RNAs (ncRNAs), several studies have examined the relationship between microRNAs and the endocannabinoid system in HCC. However, HCC is a pathological condition with high heterogeneity, and therefore using the endocannabinoid system for treatment has faced many controversies. While some studies favored a role of the endocannabinoid system in carcinogenesis and tumor induction, others exhibited the anticancer potential of endocannabinoids in HCC. In this review, specific studies delineating the relationship between endocannabinoids and HCC are examined. Based on collected findings, detailed studies of the molecular mechanism of endocannabinoids as well as preclinical studies for investigating therapeutic or carcinogenic impacts in HCC cancer are strongly suggested.

Crosstalk between lncRNAs in the apoptotic pathway and therapeutic targets in cancer.

The assertion that a significant portion of the mammalian genome has not been translated and that non-coding RNA accounts for over half of polyadenylate RNA have received much attention. In recent years, increasing evidence proposes non-coding RNAs (ncRNAs) as new regulators of various cellular processes, including cancer progression and nerve damage. Apoptosis is a type of programmed cell death critical for homeostasis and tissue development. Cancer cells often have inhibited apoptotic pathways. It has recently been demonstrated that up/down-regulation of various lncRNAs in certain types of tumors shapes cancer cells' response to apoptotic stimuli. This review discusses the most recent studies on lncRNAs and apoptosis in healthy and cancer cells. In addition, the role of lncRNAs as novel targets for cancer therapy is reviewed here. Finally, since it has been shown that lncRNA expression is associated with specific types of cancer, the potential for using lncRNAs as biomarkers is also discussed.

Crosstalk between ferroptosis and the epithelial-mesenchymal transition: Implications for inflammation and cancer therapy.

Both genomic instability and the presence of chronic inflammation are involved in carcinogenesis and tumor progression. These alterations predispose the cancer cells to undergo metabolic reprogramming as well as the epithelial-mesenchymal transition (EMT). These pathways allow cancer cells to avoid apoptosis and stimulate tumor progression. EMT is an important early event in tumor cell invasion, which can be regulated through inflammatory signaling pathways. Cancer cells undergoing EMT are vulnerable to cell death by the process of ferroptosis. Ferroptosis is a form of regulated cell death involving iron-dependent lipid peroxidation, designed to maintain cellular homeostasis. Several reports have linked ferroptosis, inflammation, and cancer. Ferroptosis inhibitors and EMT inducers have been used to understand the anti-inflammatory and anticancer effects in experimental models. A better understanding of the crosstalk between ferroptosis and EMT, and the involvment of inflammatory mediators may accelerate the discovery of therapeutic strategies to eradicate cancer cells and overcome drug-resistance.