Abnormal energy metabolism, as one of the important hallmarks of cancer, was induced by multiple carcinogenic factors and tumor-specific microenvironments. It comprises aerobic glycolysis, de novo lipid biosynthesis, and glutamine-dependent anaplerosis. Considering that metabolic reprogramming provides various nutrients for tumor survival and development, it has been considered a potential target for cancer therapy. Cannabinoids have been shown to exhibit a variety of anticancer activities by unclear mechanisms. This paper first reviews the recent progress of related signaling pathways (reactive oxygen species (ROS), AMP-activated protein kinase (AMPK), mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinase (PI3K), hypoxia-inducible factor-1alpha (HIF-1α), and p53) mediating the reprogramming of cancer metabolism (including glucose metabolism, lipid metabolism, and amino acid metabolism). Then we comprehensively explore the latest discoveries and possible mechanisms of the anticancer effects of cannabinoids through the regulation of the above-mentioned related signaling pathways, to provide new targets and insights for cancer prevention and treatment.

Intrahepatic cholangiocarcinoma is a malignant tumor originating from intrahepatic bile ducts. Surgical therapy, radiotherapy, and chemotherapy are taken to treat this disease, but it is prone to recurrence and metastasis, with poor prognosis. Therefore, it is of great significance to explore new targets and molecular mechanisms for the development of cholangiocarcinoma cells. Clinical cholangiocarcinoma tissues from patients and four human cholangiocarcinoma cell lines were analyzed for microRNA‐373 (miR‐373) expression. For investigating whether miR‐373 directly modulated unc‐51 like autophagy activating kinase 1 (ULK1), dual‐luciferase reporter assay was performed. In addition, CCK‐8 assay, flow cytometry, western blot, and immunofluorescence were applied to evaluate the proliferation, apoptosis, and autophagy of cholangiocytic hepatocellular carcinoma cells. miR‐373 downregulation was observed in clinical tissues and cell lines of cholangiocarcinoma. Overexpression of miR‐373 reduced proliferation, enhanced apoptosis, and raised expression levels of pro‐apoptosis proteins including BCL2 associated X (Bax), Caspase‐3, and Caspase‐9. Moreover, overexpression of miR‐373 downregulated expression levels of microtubule‐associated protein 1A/1B‐light chain 3 (LC3)‐II, Beclin‐1, and promoted P62 expression on mRNA and protein levels. After miR‐373 knockdown, all indexes of apoptosis and autophagy mentioned above were reversed. Luciferase activity was decreased after cotransfection of miR‐373 mimic and wild‐type ULK1 vector. Also, miR‐373 overexpression inhibited ULK1 expression. Importantly, overexpression of miR‐373 weakened expressions of ULK1, LC3, Beclin‐1, and Bcl‐2, and enhanced expressions of P62, Bax, Caspase‐3, and Caspase‐9. miR‐373 mimic treatment and subsequent ULK1 overexpression, induced reverse regulation in expressions of these proteins, compared with overexpression of miR‐373 only. miR‐373 targeted ULK1 to initiate inhibition of autophagy and subsequent promotion of apoptosis in cholangiocarcinoma cells.

Alzheimers disease (AD) is one of the acute degenerative diseases of the brain that occurs in the central nervous system. This disease is caused by the abnormal deposition of insoluble plaques and peptide amyloid beta (Aβ), the formation of nodules, and synaptic disorder. The formation of these nodes disrupts the functioning of neural circuits and changes in behavioral response due to the activation of neurotransmitter receptors. Research in recent years has shown that microRNAs play an effective role in Alzheimers disease and neurotransmitter factors. Recently, miR-107 is effective in the pathology of Alzheimers disease (AD) through the regulation of NF-κB signaling pathway. Experiments conducted using the dual luciferase method and western blot analysis also showed that miR-107 in primary neurons affects neurotransmitter factors in Alzheimers disease through the regulation of the NF-κB signaling pathway. The results showed that the reduction of miR-107 expression through the regulation of the NF-κB signaling pathway leads to the suppression of cell apoptosis in Alzheimers patients. On the other hand, increasing the expression of miR-107 leads to increasing the breaking process of Amyloid precursor protein (APP). This factor increases the production of amyloid beta (Aβ) peptide plaques and increases the expression of the BACE1 gene, which ultimately leads to the induction of apoptosis and induction of Alzheimers disease.