Background: Emerging evidence indicates that circular RNAs (circRNAs) and m⁶A RNA methylation participate in the pathogenesis and metastasis of multiple malignancies including hepatocellular carcinoma (HCC). However, it remains undocumented how circRNAs form a feedback loop with the m⁶A modification contributing to HCC. Methods: A novel hsa_circ_0017114 (circGPR137B) was identified from three pairs of primary HCC and adjacent normal tissues by circRNA expression profiling. The association of circGPR137B and miR-4739 with clinicopathological parameters and prognosis in patients with HCC was analyzed by RT-qPCR, fluorescence in situ hybridization and TCGA cohorts. The role of circGPR137B in HCC was estimated in vitro and in vivo. RT-qPCR, western blot, m⁶A dot blot, RIP, MeRIP and dual-luciferase reporter assays were used to validate the reciprocal regulation of the feedback loop among circGPR137B, miR-4739 and m⁶A demethylase FTO. Meanwhile, the expression, function and prognosis of FTO in HCC were investigated by RT-qPCR, western blot, TCGA and rescue experiments. Results: We identified a new dramatically downregulated circGPR137B in HCC tissues, and found that downregulation of circGPR137B or upregulation of miR-4739 was associated with poor prognosis in patients with HCC. Ectopic expression of circGPR137B strikingly repressed the proliferation, colony formation and invasion, whereas knockdown of circGPR137B harbored the opposite effects. Moreover, restored expression of circGPR137B inhibited tumor growth and lung metastasis in vivo. Further investigations showed that circGPR137B, co-localized with miR-4739 in the cytoplasm, acted as a sponge for miR-4739 to upregulate its target FTO, which mediated m⁶A demethylation of circGPR137B and promoted its expression. Thus, a feedback loop comprising circGPR137B/miR-4739/FTO axis was formed. FTO suppressed cell growth and indicated favorable survival in patients with HCC. Conclusion: Our results demonstrate that circGPR137B inhibits HCC tumorigenesis and metastasis through the circGPR137B/miR-4739/FTO feedback loop. This positive feedback mechanism executed by functional coupling between a circRNA sponge and an m⁶A modification event suggests a model for epigenetics.

It is generally accepted that PIWI proteins are predominately expressed in the germline but absent in somatic tissues. Their best-characterized role is to suppress transposon expression, which ensures genomic stability in the germline. However, increasing evidence has suggested that PIWI proteins are linked to the hallmarks of cancer defined by Weinberg and Hanahan, such as cell proliferation, anti-apoptosis, genomic instability, invasion and metastasis. This provides new possibilities for anticancer therapies through the targeting of PIWI proteins, which may have fewer side effects due to their potential classification as a CTA (cancer/testis antigen). Furthermore, PIWI has been proposed to act as a diagnostic and prognostic marker for many types of cancer, and even to differentiate early- and late-stage cancers. We herein summarize the latest progress in this exciting field, hoping to encourage new investigations of PIWIs in cancer biology that will help to develop new therapeutics for clinical application.

The sudden outbreak of COVID‐19 has led to more than seven thousand deaths. Unfortunately, there are no specific drugs available to cure this disease. Type 2 taste receptors (TAS2Rs) may play an important role in host defense mechanisms. Based on the idea of host‐directed therapy (HDT), we performed a negative co‐expression analysis using big data of 60 000 Affymetrix expression arrays and 5000 TCGA data sets to determine the functions of TAS2R10, which can be activated by numerous bitter substances. Excitingly, we found that the main functions of TAS2R10 involved controlling infectious diseases caused by bacteria, viruses, and parasites, suggesting that TAS2R10 is a key trigger of host defense pathways. To quickly guide the clinical treatment of 2019‐nCoV, we searched currently available drugs that are agonists of TAS2Rs. We identified many cheap, available, and safe medicines, such as diphenidol, quinine, chloroquine, artemisinin, chlorpheniramine, yohimbine, and dextromethorphan, which may target the most common symptoms caused by 2019‐nCoV. We suggest that a cocktail‐like recipe of existing bitter drugs may help doctors to fight this catastrophic disease and that the general public may drink or eat bitter substances, such as coffee, tea, or bitter vegetables, to reduce the risk of infection.

The COVID-19 (here specifically called Worldwide Acute Respiratory Syndrome, WARS) pandemic is surging worldwide. Unfortunately, no specific drug meets the urgent need to fight this pandemic, leading to thousands of deaths. The theory of host-directed therapies (HDTs) is viewed as the ideal means to rephrase the treatment of infectious diseases. However, related drugs based on this theory have not been identified. Previously, we realized that caffeine is the ligand of type 2 taste receptors (TAS2Rs), which play a critical role in host defense. Here, we gathered data on caffeine acting as an immunomodulator. Unexpectedly, we found that caffeine can fight WARS by acting on multiple organs, which may prevent the virus from entering the cell, stimulate the phagocytosis of macrophages, enhance breathing, and inhibit the cytokine storm. Thus, the immunoprotective effects of caffeine can improve the therapeutic outcomes in patients infected with coronavirus. Collectively, we report that caffeine, an FDA-approved, highly safe, inexpensive, and widely available drug, could be an excellent HDT for battling WARS.

Since the first miRNA was discovered in 1993, miRNAs have become a hotspot for biological research. In order to feed this demand, a robust method is required to detect miRNA gene expression. Development of a detection method is more difficult for miRNAs than for long RNAs, such as mRNA, owing to their small size. Existing methods have limitations; thus, new methods are required. We describe a new system for detecting miRNA expression, which can distinguish miRNA from its precursor and has single-nucleotide resolution. It has single molecule and multiplex detection potential. It may be performed as a polymerase chain reaction (PCR) method, a blotting method, or a macroarray method according to the analyst's preference. This personalized system provides a convenient tool for the detection of miRNA gene expression.