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Circular RNAs (circRNAs) are a large class of noncoding RNAs that are emerging as critical regulators of various cellular processes that are involved in the physiopathological mechanism of many human diseases, such as cardiovascular disease, atherosclerosis, diabetes mellitus, and carcinogenesis. Autophagy is a conserved and catabolic cellular process that degrades unfolded, misfolded, or damaged protein aggregates or organelles to maintain cellular homeostasis under physiological and pathological conditions. Increasing evidence has shown a link between circRNAs and autophagy that is closely related to the occurrence and development of human diseases, including cancer. In this review, we highlight recent advances in understanding the functions and mechanisms of circRNAs in the regulation of autophagy in cancer. These autophagy-related circRNAs contribute to cancer development and progression in various types of human cancer by activating or inhibiting autophagy. Cumulative research on the relationship between circRNAs and autophagy regulation provides critical insight into the essential role that circRNAs play in carcinogenesis and suggests new targets for tumor therapy., Graphical abstract, circRNAs serve as oncogenes in the regulation of many biological processes of cancer cells by activating or inhibiting autophagy. In turn, autophagy may be regulated by circRNAs in cancer. The relationship between circRNAs and autophagy provides insight into the role of circRNAs in carcinogenesis, suggesting new targets for anti-cancer therapy.

Autophagy is a conserved catabolic process involving the degradation and recycling of damaged biomacromolecules or organelles through lysosomal-dependent pathways and plays a crucial role in maintaining cell homeostasis. Consequently, abnormal autophagy is associated with multiple diseases, such as infectious diseases, neurodegenerative diseases and cancer. Currently, autophagy is considered to be a dual regulator in cancer, functioning as a suppressor in the early stage while supporting the growth and metastasis of cancer cells in the later stage and may also produce therapeutic resistance. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression at the post-transcriptional level by silencing targeted mRNA. MiRNAs have great regulatory potential for several fundamental biological processes, including autophagy. In recent years, an increasing number of studies have linked miRNA dysfunction to the growth, metabolism, migration, metastasis, and responses of cancer cells to therapy. Therefore, the study of autophagy-related miRNAs in cancer will provide insights into cancer biology and lead to the development of novel anti-cancer strategies. In the present review, we summarise the current knowledge of miRNA dysregulation during autophagy in cancer, focusing on the relationship between autophagy and miRNAs, and discuss their involvement in cancer biology and cancer treatment.

Identifying high specificity and sensitivity biomarkers has always been the focus of research in the field of non-invasive cancer diagnosis. Exosomes are extracellular vesicles with a lipid bilayer membrane that can be released by all types of cells, which contain a variety of proteins, lipids, and a variety of non-coding RNAs. Increasing research has shown that the lipid bilayer can effectively protect the nucleic acid in exosomes. In cancers, tumor cell-derived exosomal circRNAs can act on target cells or organs through the transport of exosomes, and then participate in the regulation of tumor development and metastasis. Since exosomes exist in various body fluids and circRNAs in exosomes exhibit high stability, exosomal circRNAs have the potential as biomarkers for early and minimally invasive cancer diagnosis and prognosis judgment. In this review, we summarized circRNAs and their biological roles in cancers, with the emerging value biomarkers in cancer diagnosis, disease judgment, and prognosis observation. In addition, we briefly compared the advantages of exosomal circRNAs as biomarkers and the current obstacles in the exosome isolation technology, shed light to the future development of this technology.

Although the importance of PIWI-interacting RNAs (piRNAs) in cancer has recently been recognized, studies on the role and functional mechanism of piRNAs in lung adenocarcinoma (LUAD) development and progression are limited. In this study, we identified 10 differently expressed piRNAs in LUAD tissues compared to normal tissues, among which, piR-hsa-211106 expression levels were downregulated in LUAD tissues and cell lines. Furthermore, the effects of piR-hsa-211106 on the malignant phenotypes and chemosensitivity of LUAD cells were detected by gain- and loss-of-function analyses in vitro and in vivo, which showed that piR-hsa-211106 inhibited LUAD cell proliferation, tumor growth, and migration, but promoted apoptosis. Moreover, our finding indicated that piR-hsa-211106 is a potential therapeutic target that synergistically imparts anticancer effects with a chemotherapeutic agent for LUAD-cisplatin. Further mechanistic investigation indicated that piR-hsa-211106 could bind to pyruvate carboxylase (PC) by RNA pull down and RNA immunoprecipitation assays and inhibited PC mRNA and protein expression. Our study demonstrates that piR-hsa-211106 inhibits LUAD progression by hindering the expression and function of PC and enhances chemotherapy sensitivity, suggesting that piR-hsa-211106 is a novel diagnostic and therapeutic target for LUAD.

Background X‐linked hypophosphatemic rickets (XLH) is a heterogeneous genetic phosphate wasting disorder that occupies the majority of inheritable hypophosphatemic rickets (HR). XLH is caused by loss‐of‐function mutations in the phosphate‐regulating endopeptidase gene (PHEX) located on the X chromosome. Method In this study, we performed whole‐exome sequencing (WES) on the proband to identify the causative gene. The mutations were analyzed by predictive online software, such as PolyPhen‐2. Plasmids containing the wild‐type (WT) and mutant cDNA of the candidate gene were transfected into HEK293, then, the expression, cellular localization, and glycosylation state of the candidate proteins were detected by western blot, immunostaining, and endoglycosidase H digestion. The expression and concentration of related factor were measured by RT‐PCR and ELISA. Results We identified a novel missense mutation c.2179T>C in the PHEX that results in the substitution of p.Phe727Leu (F727L). This mutation was predicted to be disease‐causing by all four predictive online software. In vitro studies demonstrated that the F727L substitution hindered the intracellular trafficking of the mutant PHEX, with ~59% of mutant PHEX protein retained in the endoplasmic reticulum (ER) and only ~16% of the mutant protein localized on the cell surface. Endoglycosidase H digestion assay showed that the mutant F727L PHEX protein was not fully glycosylated. The concentration of intact FGF23 in hFOB1.19 cell culture medium collected from the mutant PHEX group was the highest (62.9 pg/ml) compared to the WT group (32.1 pg/ml) and control group (23.5 pg/ml). Conclusion Our results confirmed that the mutant PHEX protein was lowly glycosylated and retarded within the ER, the intact FGF23 level in cell culture media caused by the mutant PHEX protein was significantly elevated compared to that of the WT group, which may explain why the single base mutation in the PHEX led to XLH syndrome in this family., In this study, we identified a novel missense mutation c.2179T>C (p.F727L) in the PHEX from an XLH family. We demonstrated that the F727L mutation decreased the glycosylation level of PHEX protein, blocked PHEX protein transport from the ER to the plasma membrane, and reduced its activity to cleave FGF23 into inactive segments, which may explain why the single base substitution c.2179T>C led to the hypophosphatemic rickets in this Chinese family.

Growing evidence suggests that alterations of gene expression including expression and activities of transcription factors are closely associated with carcinogenesis. Forkhead Box Class K (FOXK) proteins, FOXK1 and FOXK2, are a family of evolutionarily conserved transcriptional factors, which have recently been recognized as key transcriptional regulators involved in many types of cancer. Members of the FOXK family mediate a wide spectrum of biological processes, including cell proliferation, differentiation, apoptosis, autophagy, cell cycle progression, DNA damage and tumorigenesis. Therefore, the deregulation of FOXKs can affect the cell fate and they promote tumorigenesis as well as cancer progression. The mechanisms of FOXKs regulation including post-translational modifications (PTMs), microRNAs (miRNAs) and protein-protein interactions are well demonstrated. However, the detailed mechanisms of FOXKs activation and deregulation in cancer progression are still inconclusive. In this review, we summarize the regulatory mechanisms of FOXKs expression and activity, and their role in the development and progression of cancer. We have discussed whether FOXKs act as tumor suppressors/oncoproteins in tumor cells and their therapeutic applications in malignant diseases are also discussed. This review may assist in designing experimental studies involving FOXKs and it would strength the therapeutic potential of FOXKs as targets for cancers.

FOXO3a is a member of the FOXO subfamily of forkhead transcription factors that mediate a variety of cellular processes including apoptosis, proliferation, cell cycle progression, DNA damage and tumorigenesis. It also responds to several cellular stresses such as UV irradiation and oxidative stress. The function of FOXO3a is regulated by a complex network of processes, including post-transcriptional suppression by microRNAs (miRNAs), post-translational modifications (PTMs) and protein–protein interactions. FOXO3a is widely implicated in a variety of diseases, particularly in malignancy of breast, liver, colon, prostate, bladder, and nasopharyngeal cancers. Emerging evidences indicate that FOXO3a acts as a tumor suppressor in cancer. FOXO3a is frequently inactivated in cancer cell lines by mutation of the FOXO3a gene or cytoplasmic sequestration of FOXO3a protein. And its inactivation is associated with the initiation and progression of cancer. In experimental studies, overexpression of FOXO3a inhibits the proliferation, tumorigenic potential, and invasiveness of cancer cells, while silencing of FOXO3a results in marked attenuation in protection against tumorigenesis. The role of FOXO3a in both normal physiology as well as in cancer development have presented a great challenge to formulating an effective therapeutic strategy for cancer. In this review, we summarize the recent findings and overview of the current understanding of the influence of FOXO3a in cancer development and progression.