Role of exosomal circular RNAs as microRNA sponges and potential targeting for suppressing hepatocellular carcinoma growth and progression

In this editorial,we comment on the article by Lyu et al published in the recent issue of the World Journal of Gastroenterology(2023;2219-2840).Hepatocellular carcinoma(HCC)is a frequently encountered and highly aggressive primary liver cancer,which remains the third-commonest cause of cancer-related death despite the current therapeutic modalities.There is urgency in developing novel thera-peutic approaches,such as by manipulating extracellular vesicles,which con-stitute a highly heterogeneous nanoparticle population that contains various cargoes.These cargoes have a pivotal role in cell-to-cell communication and can modify the functional level of the recipient cells via their uptake by other recipient cells.Exosomal non-coding RNAs have particular evolving significance in HCC,such as circular RNAs,which have been found differentially expressed in normal hepatic and HCC tissues.The aberrations in their expression levels have a key role in the HCC development and progression and the overall prognosis.In this editorial,we will shed light on the emerging role of exosomal circular RNAs in HCC development and progression,focusing on the oncogenic or potentially tumor suppressive effect of mesenchymal stem cells-derived exosomal non-coding RNAs.

Role of autophagy in cholangiocarcinoma:An autophagy-based treatment strategy

Cholangiocarcinomas(CCAs)are diverse biliary epithelial tumours involving the intrahepatic,perihilar and distal parts of the biliary tree.The three entirely variable entities have distinct epidemiology,molecular characteristics,prognosis and strategy for clinical management.However,many cholangiocarcinoma tu-mor-cells appear to be resistant to current chemotherapeutic agents.The role of autophagy and the therapeutic value of autophagy-based therapy are largely unknown in CCA.The multistep nature of autophagy offers a plethora of re-gulation points,which are prone to be deregulated and cause different human diseases,including cancer.However,it offers multiple targetable points for designing novel therapeutic strategies.Tumor cells have evolved to use auto-phagy as an adaptive mechanism for survival under stressful conditions such as energy imbalance and hypoxic region of tumors within the tumor microenvir-onment,but also to increase invasiveness and resistance to chemotherapy.The purpose of this review is to summarize the current knowledge regarding the interplay between autophagy and cholangiocarcinogenesis,together with some preclinical studies with agents that modulate autophagy in order to induce tumor cell death.Altogether,a combinatorial strategy,which comprises the current anti-cancer agents and autophagy modulators,would represent a positive CCA patient approach.

Implication of gut microbiome in immunotherapy for colorectal cancer

Colorectal cancer(CRC) constitutes the third most frequently reported malignancy in the male population and the second most common in women in the last two decades. Colon carcinogenesis is a complex, multifactorial event, resulting from genetic and epigenetic aberrations, the impact of environmental factors, as well as the disturbance of the gut microbial ecosystem. The relationship between the intestinal microbiome and carcinogenesis was relatively undervalued in the last decade. However, its remarkable effect on metabolic and immune functions on the host has been in the spotlight as of recent years. There is a strong relationship between gut microbiome dysbiosis, bowel pathogenicity and responsiveness to anti-cancer treatment;including immunotherapy. Modifications of bacteriome consistency are closely associated with the immunologic response to immunotherapeutic agents. This condition that implies the necessity of gut microbiome manipulation. Thus, creatingan optimal response for CRC patients to immunotherapeutic agents. In this paper, we will review the current literature observing how gut microbiota influence the response of immunotherapy on CRC patients.