Exosomal hsa_circ_000200 as a potential biomarker and metastasis enhancer of gastric cancer via miR-4659a/b-3p/HBEGF axis.

BACKGROUND: Exosome, a component of liquid biopsy, loaded protein, DNA, RNA and lipid gradually emerges as biomarker in tumors. However, exosomal circRNAs as biomarker and function mechanism in gastric cancer (GC) are not well understood. METHODS: Differentially expressed circRNAs in GC and healthy people were screened by database. The identification of hsa_circ_000200 was verified by RNase R and sequencing, and the expression of hsa_circ_000200 was evaluated using qRT-PCR. The biological function of hsa_circ_000200 in GC was verified in vitro. Western blot, RIP, RNA fluorescence in situ hybridization, and double luciferase assay were utilized to explore the potential mechanism of hsa_circ_000200. RESULTS: Hsa_circ_000200 up-regulated in GC tissue, serum and serum exosomes. Hsa_circ_000200 in serum exosomes showed better diagnostic ability than that of tissues and serum. Combined with clinicopathological parameters, its level was related to invasion depth, TNM staging, and distal metastasis. Functionally, knockdown of hsa_circ_000200 inhibited GC cells proliferation, migration and invasion in vitro, while its overexpression played the opposite role. Importantly, exosomes with up-regulated hsa_circ_000200 promoted the proliferation and migration of co-cultured GC cells. Mechanistically, hsa_circ_000200 acted as a "ceRNA" for miR-4659a/b-3p to increase HBEGF and TGF-ß/Smad expression, then promoted the development of GC. CONCLUSIONS: Our findings suggest that hsa_circ_000200 promotes the progression of GC through hsa_circ_000200/miR-4659a/b-3p/HBEGF axis and affecting the expression of TGF-ß/Smad. Serum exosomal hsa_circ_000200 may serve as a potential biomarker for GC.

Tuning Dehalogenative Coupling of Br2Py on Bimetallic Templates.

Considerable attention has been paid to on-surface Ullmann coupling during the past decade owing to the feasible synthesis of artificial nanostructures. While previous reports mainly concentrated on coupling reactions on single-metal-atom surfaces, herein we present the Ullmann coupling of 2,7-dibromopyrene (Br2Py) on bimetallic surfaces, Bi-Ag(111) and Bi-Au(111), respectively, with scanning tunneling microscopy (STM) and X-ray photoemission spectroscopy (XPS). On the Bi-decorated Ag(111), self-assembly of intact Br2Py is realized due to the reduced activity at the interface. Subsequent annealing promotes the dehalogenation of Br2Py on Bi-Ag(111), while Bi adatoms do not bring any visible influence on coupling reactions. Furthermore, post-deposition of Bi onto preassembled nanostructures on Ag(111) immediately initiates the Ullmann coupling by inducing more Ag adatoms available on the surface, while stepwise annealing afterward leads to complete polymerization and formation of covalent chains with lateral displacement compared to that on the bare Ag(111), probably due to the space hindrance and confinement. For Bi-Au(111) with the modified reconstruction, higher-temperature annealing is required to trigger Ullmann coupling compared to that on Au(111). The exception is that the C-C coupling reaction remains impervious to Bi adatoms, and recovery of the Bi-Au reconstruction is realized after intensive annealing. In principle, bimetallic surfaces herein present intriguing behavior toward the controllable Ullmann coupling, and this report might provide different insights into the comprehensive atomistic elucidation of reaction mechanisms as well as the design of a new platform to effectively regulate Ullmann coupling.

Modulation of miR-34a in curcumin-induced antiproliferation of prostate cancer cells.

Curcumin is a phytochemical which exhibits significant inhibitory effect in multiple cancers including prostate cancer. MicroRNA-34a (miR-34a) was found to be a master tumor suppressor miRNA and regulated the growth of cancer cells. To date, however, the role of miR-34a in the anticancer action of curcumin against prostate cancer has been rarely reported. In the present study, we showed that curcumin altered the expression of cell cycle-related genes (cyclin D1, PCNA, and p21) and inhibited the proliferation of prostate cancer cells. Furthermore, we found that curcumin significantly upregulated the expression of miR-34a, along with the downregulated expression of ß-catenin and c-myc in three prostate cancer cell lines. Inhibition of miR-34a activated ß-catenin/c-myc axis, altered cell cycle-related genes expression and significantly suppressed the antiproliferation effect of curcumin in prostate cancer cells. Findings from this study revealed that miR-34a plays an important role in the antiproliferation effect of curcumin in prostate cancer.

UBR2 Enriched in p53 Deficient Mouse Bone Marrow Mesenchymal Stem Cell-Exosome Promoted Gastric Cancer Progression via Wnt/ß-Catenin Pathway.

The deficiency or mutation of p53 has been linked to several types of cancers. The mesenchymal stem cell (MSC) is an important component in the tumor microenvironment, and exosomes secreted by MSCs can transfer bioactive molecules, including proteins and nucleic acid, to other cells in the tumor microenvironment to influence the progress of a tumor. However, whether the state of p53 in MSCs can impact the bioactive molecule secretion of exosomes to promote cancer progression and the regulatory mechanism remains elusive. Our study aimed to investigate the regulation of ubiquitin protein ligase E3 component n-recognin 2 (UBR2) enriched in exosomes secreted by p53 deficient mouse bone marrow MSC (p53-/- mBMMSC) in gastric cancer progression in vivo and in vitro. We found that the concentration of exosome was significantly higher in p53-/- mBMMSC than that in p53 wild-type mBMMSC (p53+/+ mBMMSC). In particular, UBR2 was highly expressed in p53-/- mBMMSC cells and exosomes. P53-/- mBMMSC exosomes enriched UBR2 could be internalized into p53+/+ mBMMSC and murine foregastric carcinoma (MFC) cells and induce the overexpression of UBR2 in these cells which elevated cell proliferation, migration, and the expression of stemness-related genes. Mechanistically, the downregulation of UBR2 in p53-/- mBMMSC exosomes could reverse these actions. Moreover, a majority of Wnt family members, ß-catenin, and its downstream genes (CD44, CyclinD1, CyclinD3, and C-myc) were significantly decreased in MFC knockdown UBR2 and ß-catenin depletion, an additional depletion of UBR2 had no significant difference in the expression of Nanog, OCT4, Vimentin, and E-cadherin. Taken together, our findings indicated that p53-/- mBMMSC exosomes could deliver UBR2 to target cells and promote gastric cancer growth and metastasis by regulating Wnt/ß-catenin pathway. Stem Cells 2017;35:2267-2279.

Effects of Curcumin on Tobacco Smoke-induced Hepatic MAPK Pathway Activation and Epithelial-Mesenchymal Transition In Vivo.

Tobacco smoke is a major risk factor for hepatic cancer. Epithelial-mesenchymal transition (EMT) induced by tobacco smoke is crucially involved in the initiation and development of cancer. Mitogen-activated protein kinase (MAPK) pathways play important roles in tobacco smoke-associated carcinogenesis including EMT process. The chemopreventive effect of curcumin supplementation against cancers has been reported. In this study, we investigated the effects of tobacco smoke on MAPK pathway activation and EMT alterations, and then the preventive effect of curcumin was examined in the liver of BALB/c mice. Our results indicated that exposure of mice to tobacco smoke for 12 weeks led to activation of ERK1/2, JNK, p38 and ERK5 pathways as well as activator protein-1 (AP-1) proteins in liver tissue. Exposure of mice to tobacco smoke reduced the hepatic mRNA and protein expression of the epithelial markers, while the hepatic mRNA and protein levels of the mesenchymal markers were increased. Treatment of curcumin effectively attenuated tobacco smoke-induced activation of ERK1/2 and JNK MAPK pathways, AP-1 proteins and EMT alterations in the mice liver. Our data suggested the protective effect of curcumin in tobacco smoke-triggered MAPK pathway activation and EMT in the liver of BALB/c mice, thus providing new insights into the chemoprevention of tobacco smoke-associated hepatic cancer. Copyright © 2017 John Wiley & Sons, Ltd.

Folic Acid Protected Neural Cells Against Aluminum-Maltolate-Induced Apoptosis by Preventing miR-19 Downregulation.

Aluminum (Al)-induced apoptosis is considered as the major cause of its neurotoxicity. Folic acid possesses neuroprotective function by preventing neural cell apoptosis. microRNAs (miRNAs) are important regulators of gene expression participating in cellular processes. As a key component of the miR-17-92 cluster, miR-19 is implicated in regulating apoptotic process, while its role in the neuroprotective effect of folic acid has not been investigated. The present study aimed to investigate the potential involvement and function of miR-19 in the protective action of folic acid against Al-induced neural cell apoptosis. Human SH-SY5Y cells were treated with Al-maltolate (Al-malt) in the presence or absence of folic acid. Results showed that Al-malt-induced apoptosis of SH-SY5Y cells was effectively prevented by folic acid. Al-malt suppressed the expression of miR-19a/19b, along with alterations of miR-19 related apoptotic proteins including PTEN, p-AKT, p53, Bax, Bcl-2, caspase 9 and caspase 3; and these effects were ameliorated by folic acid. miR-19 inhibitor alone induced apoptosis of SH-SY5Y cells. Combination treatment of folic acid and miR-19 inhibitor diminished the neuroprotective effect of folic acid. These findings demonstrated that folic acid protected neuronal cells against Al-malt-induced apoptosis by preventing the downregulation of miR-19 and modulation of miR-19 related downstream PTEN/AKT/p53 pathway.

Medium-chain triglyceride ameliorates insulin resistance and inflammation in high fat diet-induced obese mice.

PURPOSE: The aim of the present study was to investigate the in vivo effects of dietary medium-chain triglyceride (MCT) on inflammation and insulin resistance as well as the underlying potential molecular mechanisms in high fat diet-induced obese mice. METHODS: Male C57BL/6J mice (n = 24) were fed one of the following three diets for a period of 12 weeks: (1) a modified AIN-76 diet with 5 % corn oil (normal diet); (2) a high-fat control diet (17 % w/w lard and 3 % w/w corn oil, HFC); (3) an isocaloric high-fat diet supplemented with MCT (17 % w/w MCT and 3 % w/w corn oil, HF-MCT). Glucose metabolism was evaluated by fasting blood glucose levels and intraperitoneal glucose tolerance test. Insulin sensitivity was evaluated by fasting serum insulin levels and the index of homeostasis model assessment-insulin resistance. The levels of serum interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α were measured by ELISA, and hepatic activation of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways was determined using western blot analysis. RESULTS: Compared to HFC diet, consumption of HF-MCT did not induce body weight gain and white adipose tissue accumulation in mice. HFC-induced increases in serum fasting glucose and insulin levels as well as glucose intolerance were prevented by HF-MCT diet. Meanwhile, HF-MCT resulted in significantly lower serum IL-6 level and higher IL-10 level, and lower expression levels of inducible nitric oxide synthase and cyclooxygenase-2 protein in liver tissues when compared to HFC. In addition, HF-MCT attenuated HFC-triggered hepatic activation of NF-κB and p38 MAPK. CONCLUSIONS: Our study demonstrated that MCT was efficacious in suppressing body fat accumulation, insulin resistance, inflammatory response, and NF-κB and p38 MAPK activation in high fat diet-fed mice. These data suggest that MCT may exert beneficial effects against high fat diet-induced insulin resistance and inflammation.

Benzidine induces epithelial-mesenchymal transition in human uroepithelial cells through ERK1/2 pathway.

Prolonged benzidine exposure is a known cause of urothelial carcinoma (UC). Benzidine-induced epithelial-to-mesenchymal transition (EMT) is critically involved in cell malignant transformation. The role of ERK1/2 in regulating benzidine-triggered EMT has not been investigated. This study was to investigate the regulatory role of ERK1/2 in benzidine-induced EMT. By using wound healing and transwell chamber migration assays, we found that benzidine could increase SV-HUC-1 cells invasion activity, western blotting and Immunofluorescence showed that the expression levels of Snail, ß-catenin, Vimentin, and MMP-2 were significantly increased, while, the expression levels of E-cadherin, ZO-1 were decreased. To further demonstrate the mechanism in this process, we found that the phosphorylation of ERK1/2, p38, JNK and AP-1 proteins were significantly enhanced compared to the control group (*P < 0.05). Afterward, treated with MAPK pathways inhibitors, only ERK inhibitor（U0126）could reduce the expression of EMT markers in SV-HUC-1 cells, but not p38 and JNK inhibitor（SB203580, SP600125）, which indicated that benzidine induces the epithelial-mesenchymal transition in human uroepithelial cells through ERK1/2 pathway. Taken together, findings from this study could provide into the molecular mechanisms by which benzidine exerts its bladder-cancer-promoting effect as well as its target intervention.

Curcumin Suppresses MAPK Pathways to Reverse Tobacco Smoke-induced Gastric Epithelial-Mesenchymal Transition in Mice.

Tobacco smoke (TS) has been shown to cause gastric cancer. Epithelial-mesenchymal transition (EMT) is a crucial pathophysiological process in cancer development. Mitogen-activated protein kinase (MAPK) pathways play central roles in tumorigenesis including EMT process. Curcumin is a promising chemopreventive agent for several types of cancers. In the present study, we investigated the effects of TS on MAPK pathway activation and EMT alterations in the stomach of mice, and the preventive effect of curcumin was further examined. Results showed that exposure of mice to TS for 12 weeks resulted in activation of extracellular regulated protein kinases 1 and 2 (ERK1/2), the Jun N-terminal kinase (JNK), p38, and ERK5 MAPK pathways as well as activator protein 1 (AP-1) proteins in stomach. TS reduced the mRNA and protein expression levels of the epithelial markers E-cadherin and ZO-1, while the mRNA and protein expression levels of the mesenchymal markers vimentin and N-cadherin were increased. Treatment of curcumin effectively abrogated TS-triggered gastric activation of ERK1/2 and JNK MAPK pathways, AP-1 proteins, and EMT alterations. These results suggest for the first time the protective effects of curcumin in long-term TS exposure-induced gastric MAPK activation and EMT, thus providing new insights into the pathogenesis and chemoprevention of TS-associated gastric cancer.

Curcumin modulates miR-19/PTEN/AKT/p53 axis to suppress bisphenol A-induced MCF-7 breast cancer cell proliferation.

Breast cancer is the most common cancer in women. Bisphenol A (BPA), as a known endocrine disrupter, is closely related to the development of breast cancer. Curcumin has been clinically used in chemopreventation and treatment of cancer; however, it remains unknown whether microRNAs are involved in curcumin-mediated protection from BPA-associated promotive effects on breast cancer. In the present study, we showed that BPA exhibited estrogenic activity by increasing the proliferation of estrogen-receptor-positive MCF-7 human breast cancer cells and triggering transition of the cells from G1 to S phase. Curcumin inhibited the proliferative effects of BPA on MCF-7 cells. Meanwhile, BPA-induced upregulation of oncogenic miR-19a and miR-19b, and the dysregulated expression of miR-19-related downstream proteins, including PTEN, p-AKT, p-MDM2, p53, and proliferating cell nuclear antigen, were reversed by curcumin. Furthermore, the important role of miR-19 in BPA-mediated MCF-7 cell proliferation was also illustrated. These results suggest for the first time that curcumin modulates miR-19/PTEN/AKT/p53 axis to exhibit its protective effects against BPA-associated breast cancer promotion. Findings from this study could provide new insights into the molecular mechanisms by which BPA exerts its breast-cancer-promoting effect as well as its target intervention.

The role of m6A modified circ0049271 induced by MNNG in precancerous lesions of gastric cancer.

Gastric cancer (GC) is a malignant cancer with the highest global rates of morbidity and death. Dietary factors have a close relationship with the occurrence of GC. Circular RNAs (circRNAs) and N6-methyladenine (m6A) are important factors in the onset and progression of GC and other malignancies. However, little is known about the role of circRNA m6A modifications in the occurrence and development of GC. Initially, a transformed malignant cell model generated by the chemical carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was established in this investigation. Furthermore, following exposure to MNNG, circ0049271 is substantially expressed in gastric epithelial cells (GES-1). Subsequent research revealed that the knockdown of circ0049271 prevented the epithelial-mesenchymal transition (EMT) as well as the migration, invasion, and proliferation of gastric epithelial cells induced by long-term exposure to MNNG. The opposite effects were observed when circ0049271 was overexpressed. Mechanistically, circ0049271 activates the TGFß/SMAD signaling pathway and has m6A modifications mediated by WTAP. Our findings indicate that circ0049271 promotes the occurrence of GC by regulating the TGFß/SMAD pathway, and WTAP may mediate the methylation of circ0049271 m6A. This study provides new insights into the regulation of circRNA-mediated m6A modifications and the discovery of early GC induced by dietary factors such as nitrite.

Novel role of circRNAs in the drug resistance of gastric cancer: regulatory mechanisms and future for cancer therapy.

Cancer, including gastric cancer, has become a serious disease that jeopardizes public life. Currently, the main treatment methods are surgery, radiation therapy, and chemotherapy. One of the primary causes of death for patients with gastric cancer is drug resistance. Several mechanisms of anticancer drugs resistance have been reported, including changes in drugs transport and metabolism, mutations in drug targets, changes in DNA repair systems, inhibition of cell apoptosis and autophagy, gastric cancer stem cells, invasion and migration. It is becoming more widely known that non-coding RNAs, like circRNAs, play a critical role in the resistance of drugs used to treat gastric cancer. CircRNAs have a unique structure and function that is related to gastric cancer resistance, cell proliferation, apoptosis, autophagy, DNA repair systems, migration, and invasion. A clear understanding of the molecular mechanism of circRNAs mediated the resistance of gastric cancer drugs will open a new window for the treatment and management of gastric cancer. Therefore, in this review, we will summarize the current mechanism of drug resistance, and finally discuss the molecular mechanism of circRNAs in regulating the development of drug resistance in gastric cancer.

Corrigendum: Anticancer applications of phytochemicals in gastric cancer: effects and molecular mechanism.

[This corrects the article DOI: 10.3389/fphar.2022.1078090.].

Constructing Molecular Networks on Metal Surfaces through Tellurium-Based Chalcogen-Organic Interaction.

On-surface molecular self-assembly presents an important approach to the development of low-dimensional functional nanostructures and nanomaterials. Traditional strategies primarily exploit hydrogen bonding or metal coordination, yet the potential of chalcogen bonding (ChB) for on-surface self-assemblies remains underexplored. Here, we explore fabricating molecular networks via tellurium (Te)-directed chalcogen-organic interactions. Employing carbonitrile molecules as molecular building blocks, we have achieved extended 2D networks exhibiting a 4-fold binding motif on Au(111), marking a notable difference from the conventional coordinative interaction involving transition metals. Our findings, supported by density functional theory (DFT) and scanning tunneling spectroscopy (STS), show that the Te-carbonitrile interaction exhibits lower stability compared to the metal-organic coordination, and the construction of the Te-directed molecular networks does not alter the electronic properties of the involved molecules. Introducing chalcogen-directed interactions may expand the spectrum of strategies in supramolecular assembly, contributing to the design of advanced molecular architectures for nanotechnological applications.

Exosomal circRNAs in gastrointestinal cancer: Role in occurrence, development, diagnosis and clinical application (Review).

Gastrointestinal cancer is frequently detected at an advanced stage and has an undesirable prognosis due to the absence of efficient and precise biomarkers and therapeutic targets. Exosomes are small, living­cell­derived vesicles that serve a critical role in facilitating intercellular communication by transporting molecules from donor cells to receiver cells. circular RNAs (circRNAs) are mis­expressed in a variety of diseases, including gastrointestinal cancer, and are promising as diagnostic biomarkers and tumor therapeutic targets for gastrointestinal cancer. The main features of exosomes and circRNAs are discussed in the present review, along with research on the biological function of exosomal circRNAs in the development and progression of gastrointestinal cancer. It also assesses the advantages and disadvantages of implementing these findings in clinical applications.

Hesperidin inhibits tobacco smoke-induced pulmonary cell proliferation and EMT in mouse lung tissues via the p38 signaling pathway.

Tobacco smoke (TS) is the major cause of lung cancer. The abnormal proliferation and epithelial-mesenchymal transition (EMT) of lung cells promote occurrence and development of lung cancer. The p38 pathway intervenes in this cancer development. Hesperidin also serves a role in human health and disease prevention. The roles of p38 in TS-mediated abnormal cell proliferation and EMT, and the hesperidin intervention thereof are not yet understood. In the present study, it was demonstrated that TS upregulated proliferating cell nuclear antigen, vimentin and N-cadherin expression, whereas it downregulated E-cadherin expression, as assessed using western blotting and reverse transcription-quantitative PCR. Furthermore, it was observed that inhibition of the p38 pathway inhibit TS-induced proliferation and EMT. Hesperidin treatment prevented the TS-induced activation of the p38 pathway, EMT and cell proliferation in mouse lungs. The findings of the present study may provide insights into the pathogenesis of TS-related lung cancer.

Cigarette Smoke-Induced Gastric Cancer Cell Exosomes Affected the Fate of Surrounding Normal Cells via the Circ0000670/Wnt/ß-Catenin Axis.

Cigarette smoke is a major risk factor for gastric cancer. Exosomes are an important part of intercellular and intra-organ communication systems and can carry circRNA and other components to play a regulatory role in the occurrence and development of gastric cancer. However, it is unclear whether cigarette smoke can affect exosomes and exosomal circRNA to promote the development of gastric cancer. Exosomes secreted by cancer cells promote cancer development by affecting surrounding normal cells. Herein, we aimed to clarify whether the exosomes secreted by cigarette smoke-induced gastric cancer cells can promote the development of gastric cancer by affecting the surrounding gastric mucosal epithelial cells (GES-1). In the present study, we treated gastric cancer cells with cigarette smoke extract for 4 days and demonstrated that cigarette smoke promotes the stemness and EMT of gastric cancer cells and cigarette smoke-induced exosomes promote stemness gene expression, EMT processes and the proliferation of GES-1 cells. We further found that circ0000670 was up-regulated in tissues of gastric cancer patients with smoking history, cigarette smoke-induced gastric cancer cells and their exosomes. Functional assays showed that circ0000670 knockdown inhibited the promoting effects of cigarette smoke-induced exosomes on the stemness and EMT characteristic of GES-1 cells, whereas its overexpression had the opposite effect. In addition, exosomal circ0000670 was found to promote the development of gastric cancer by regulating the Wnt/ß-catenin pathway. Our findings indicated that exosomal circ0000670 promotes cigarette smoke-induced gastric cancer development, which might provide a new basis for the treatment of cigarette smoke-related gastric cancer.

On-Surface Synthesis of Pentagon-Incorporated Graphene-Like Nanoribbons with Multiple Precursors.

Graphene nanoribbons (GNRs) and their derivatives are receiving increasing attention as a result of their unique electronic and magnetic properties, and many novel derivative structures have been fabricated. The carbon pentagon plays a crucial role in determining both geometric structures and electronic properties of carbon-based materials. Here, we demonstrate that carbon-pentagon-incorporated graphene-like nanoribbons (GLNRs), which are an important class of GNR derivatives, are successfully fabricated via the Ullmann coupling and aromatic cyclodehydrogenation reaction on the surface by a suitable choice of multiple tailored molecular precursors. Our approach provides a basis for the impact of adatoms in the reaction and proves the steering function of the aryl-metal interaction in procedures of self-assembly and organometallic state. In addition, this study paves the way for on-surface synthesis of GNRs and their derivatives as well as the fine tuning of electronic properties of carbon nanoarchitectures by manipulating the edge structures and embedding carbon pentagon heterojunctions.

Chirality variation from self-assembly on Ullmann coupling for the DBCh adsorbate on Au(111) and Ag(111).

On-surface Ullmann coupling has been considered an appealing approach for the precise fabrication of carbon-based covalent nanostructures under solution-free conditions. However, chirality has seldom been discussed in Ullmann reactions. In this report, self-assembled two-dimensional chiral networks are initially constructed in a large area on Au(111) and Ag(111) after adsorption of the prochiral precursor, 6,12-dibromochrysene (DBCh). Self-assembled phases are then transformed into organometallic (OM) oligomers after debromination, preserving the chirality; in particular, the formation of scarcely reported OM species on Au(111) is discovered herein. With the aryl-aryl bonding induced after intensive annealing, covalent chains are fabricated via the cyclodehydrogenation between chrysene blocks, resulting in the formation of 8-armchair graphene nanoribbons with staggered valleys on both sides. Before chiral polymer chains are constructed by chrysene blocks, the high structural flexibility of OM intermediates on Ag(111) is also revealed during reactions, which is derived from the twofold coordination of Ag atoms and conformationally flexible metal-carbon bonding. Our report not only provides solid evidence of atomically precise fabrication of covalent nanostructures with a feasible bottom-up approach but also sheds insights into the comprehensive investigation of chirality variation from monomers to artificial architectures via surface coupling reactions.

Autophagy Related Noncoding RNAs: Emerging Regulatory Factors of Gastric Cancer.

Gastric cancer (GC) is one of the most common malignant cancers that seriously affect human health. Autophagy is a highly conserved self-defense mechanism found to plays an important role in the occurrence, progression, drug resistance, and prognosis of GC. Noncoding RNAs (ncRNAs) play a critical role in the occurrence and development of a variety of diseases including GC. In recent years, increasing attention has been given to research on autophagy-related ncRNAs, such as miRNA, lncRNA, and circRNA in GC. Herein, we briefly summarize the roles, functions, and the research progress of autophagy and autophagy-related ncRNAs in GC with a focus on the potential application in GC tumorigenesis, development, prognosis, and drug resistance. We also discussed prospects of clinical application, future research direction, and challenges in future research of autophagy-related ncRNAs.