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Cytoplasmic polyadenylation element-binding protein 3 (CPEB3) is a sequence-specific RNA-binding protein. We had reported that CPEB3 is involved in hepatocellular carcinoma (HCC) progression. However, the underlying mechanisms of CPEB3 in HCC remain unclear. In this study, we firstly performed RNA immunoprecipitation to uncover the transcriptome-wide CPEB3-bound mRNAs (CPEB3 binder) in HCC. Bioinformatic analysis indicates that CPEB3 binders are closely related to cancer progression, especially HCC metastasis. Further studies confirmed that metadherin (MTDH) is a direct target of CPEB3. CPEB3 can suppress the translation of MTDH mRNA in vivo and in vitro. Besides, luciferase assay demonstrated that CPEB3 interacted with 3'-untranslated region of MTDH mRNA and inhibited its translation. Subsequently, CPEB3 inhibited the epithelial-mesenchymal transition and metastasis of HCC cells through post-transcriptional regulation of MTDH. In addition, cpeb3 knockout mice are more susceptible to carcinogen-induced hepatocarcinogenesis and subsequent lung metastasis. Our results also indicated that CPEB3 was a good prognosis marker, which is downregulated in HCC tissue. In conclusion, our results demonstrated that CPEB3 played an important role in HCC progression and targeting CPEB3-mediated mRNA translation might be a favorable therapeutic approach.Contextualisation of the new type of cell death called "ferroptosis" opened a completely new avenue for the development of anti-cancer therapies. Cumulative fundamental research dating back to the mid-20th century, crowned by the extraordinary work of the group led by Dr. Stockwell from Columbia University in 2012, finally got its candidature to be applied in the clinical settings. this website Although the potential for clinical importance is undoubtedly growing every day, as showed by the increasing number of papers dealing with ferroptosis and its applications, long experience of cancer research and treatment taught us that caution is still necessary. The plasticity of the tumour cells, particularly acute, along with its involvement in the resistance mechanisms, that have been seen, to greater or lesser extent, for almost all currently used therapies, represents the biggest fascinations in biomedical research field and also the biggest challenge to achieving cures in cancer patients. Accordingly, the main features of fundamental research have to be vigilance and anticipation. In this review, we tried to summarize the literature data, accumulated in the past couple of years, which point out the pitfalls in which "ferroptosis inducers" can fall if used prematurely in the clinical settings, but at the same time can provide a great advantage in the exhausting battle with cancer resistance. This is the first comprehensive review focusing on the effects of the cell-to-cell contact/interplay in the development of resistance to ferroptosis, while the contribution of cell-born factors has been summarized previously so here we just listed them.The consumption of red meat is probably carcinogenic to humans and is associated with an increased risk to develop colorectal cancer (CRC). Red meat contains high amounts of heme iron, which is thought to play a causal role in tumor formation. In this study, we investigated the genotoxic and cytotoxic effects of heme iron (i.e., hemin) versus inorganic iron in human colonic epithelial cells (HCEC), human CRC cell lines and murine intestinal organoids. Hemin catalyzed the formation of reactive oxygen species (ROS) and induced oxidative DNA damage as well as DNA strand breaks in both HCEC and CRC cells. In contrast, inorganic iron hardly affected ROS levels and only slightly increased DNA damage. Hemin, but not inorganic iron, caused cell death and reduced cell viability. This occurred preferentially in non-malignant HCEC, which was corroborated in intestinal organoids. Both hemin and inorganic iron were taken up into HCEC and CRC cells, however with differential kinetics and efficiency. Hemin caused stabilization and nuclear translocation of Nrf2, which induced heme oxygenase-1 (HO-1) and ferritin heavy chain (FtH). This was not observed after inorganic iron treatment. Chemical inhibition or genetic knockdown of HO-1 potentiated hemin-triggered ROS generation and oxidative DNA damage preferentially in HCEC. Furthermore, HO-1 abrogation strongly augmented the cytotoxic effects of hemin in HCEC, revealing its pivotal function in colonocytes and highlighting the toxicity of free intracellular heme iron. Taken together, this study demonstrated that hemin, but not inorganic iron, induces ROS and DNA damage, resulting in a preferential cytotoxicity in non-malignant intestinal epithelial cells. Importantly, HO-1 conferred protection against the detrimental effects of hemin.Following publication, the authors asked to add the following institution to the affiliations of author Madoka Matsushita Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Both the PDF and HTML versions of the Article have been updated accordingly.Bone marrow-derived mesenchymal stem cells (BMSCs) in postmenopausal osteoporosis models exhibit loss of viability and multipotency. Identification of the differentially expressed RNAs in osteoporotic BMSCs could reveal the mechanisms underlying BMSC dysfunction under physiological conditions, which might improve stem cell therapy and tissue regeneration. In this study, we performed high-throughput RNA sequencing and showed that the novel long non-coding RNA (lncRNA) LNC_000052 and its co-expressed mRNA PIK3R1 were upregulated in osteoporotic BMSCs. Knockdown of LNC_000052 could promote BMSC proliferation, migration, osteogenesis, and inhibit apoptosis via the PI3K/Akt signaling pathway. We found that both LNC_000052 and PIK3R1 shared a miRNA target, miR-96-5p, which was downregulated in osteoporotic BMSCs. Their binding sites were confirmed by dual-luciferase assays. Downregulation of miR-96-5p could restrain the effects of LNC_000052 knockdown while upregulation of miR-96-5p together with LNC_000052 knockdown could improve the therapeutic effects of BMSCs. In summary, the LNC_000052-miR-96-5p-PIK3R1 axis led to dysfunction of osteoporotic BMSCs and might be a novel therapeutic target for stem cell therapy and tissue regeneration.