Progression Of Gastrointestinal Cancers Research Articles

Exosomal LncRNAs in Gastrointestinal Cancer: Biological Functions and Emerging Clinical Applications.

Due to the lack of specific and effective biomarkers and therapeutic targets, the early diagnosis and treatment of gastrointestinal cancer remain unsatisfactory. As a type of nanosized vesicles derived from living cells, exosomes mediate cell-to-cell communication by transporting bioactive molecules, thus participating in the regulation of many pathophysiological processes. Recent evidence has revealed that several long non-coding RNAs (lncRNAs) are enriched in exosomes. Exosomes-mediated lncRNAs delivery is critically involved in various aspects of gastrointestinal cancer progression, such as tumor proliferation, metastasis, angiogenesis, stemness, immune microenvironment, and drug resistance. Exosomal lncRNAs represent promising candidates to act as the diagnosis biomarkers and anti-tumor targets. This review introduces the major characteristics of exosomes and lncRNAs and describes the biological functions of exosomal lncRNAs in gastrointestinal cancer development. The preclinical studies on using exosomal lncRNAs to monitor and treat gastrointestinal cancer are also discussed, and the opportunities and challenges for translating them into clinical practice are evaluated.

Nanotechnology and machine learning enable circulating tumor cells as a reliable biomarker for radiotherapy responses of gastrointestinal cancer patients

A highly sensitive, circulating tumor cell (CTC)-based liquid biopsy was used to monitor gastrointestinal cancer patients during treatment to determine if CTC abundance was predictive of disease recurrence. The approach used a combination of biomimetic cell rolling on recombinant E-selectin and dendrimer-mediated multivalent immunocapture at the nanoscale to purify CTCs from peripheral blood mononuclear cells. Due to the exceptionally high numbers of CTCs captured, a machine learning algorithm approach was developed to efficiently and reliably quantify abundance of immunocytochemically-labeled cells. A convolutional neural network and logistic regression model achieved 82.9% true-positive identification of CTCs with a false positive rate below 0.1% on a validation set. The approach was then used to quantify CTC abundance in peripheral blood samples from 27 subjects before, during, and following treatments. Samples drawn from the patients either prior to receiving radiotherapy or early in chemotherapy had a median 50 CTC ml−1 whole blood (range 0.6–541.6). We found that the CTC counts drawn 3 months post treatment were predictive of disease progression (p = .045). This approach to quantifying CTC abundance may be a clinically impactful in the timely determination of gastrointestinal cancer progression or response to treatment.

Exosomes as drug delivery system in gastrointestinal cancer.

Gastrointestinal cancer is one of the most common malignancies with relatively high morbidity and mortality. Exosomes are nanosized extracellular vesicles derived from most cells and widely distributed in body fluids. They are natural endogenous nanocarriers with low immunogenicity, high biocompatibility, and natural targeting, and can transport lipids, proteins, DNA, and RNA. Exosomes contain DNA, RNA, proteins, lipids, and other bioactive components, which can play a role in information transmission and regulation of cellular physiological and pathological processes during the progression of gastrointestinal cancer. In this paper, the role of exosomes in gastrointestinal cancers is briefly reviewed, with emphasis on the application of exosomes as drug delivery systems for gastrointestinal cancers. Finally, the challenges faced by exosome-based drug delivery systems are discussed.

The Evaluation of HERV-K np9, rec, gag Expression in Isolated Human Peripheral Blood Mononuclear Cell (PBMC) of Gastric and Colon Cancer

Background: In the current age of diagnostic approaches in cancer, countless efforts have been allocated to identify novel and efficient biomarkers to detect cancer in its early stages. We focused on evaluating the correlation between the progression of gastrointestinal cancer, a leading cause of cancer death worldwide, and human endogenous retrovirus (HERV). Materials and Methods: In this study, we conducted a study on the peripheral blood mononuclear cells (PBMC) gathered from gastric and colon cancer patients. We focused on HERV-K rec, np9, gag expression analysis by quantitative real-time PCR, after extraction of RNA and synthesizing cDNA. Results: Unlike np9 whose expression increased significantly in the colon and gastric cancers, the mRNA level of the rec gene declined in both cancers. Moreover, our data illustrated that the over-expression of the gag gene was only observed in colon cancerous cells rather than gastric malignancy. Conclusions: Overall, given the correlation between the expression level of HERV-associated genes and gastrointestinal cancer, our study suggests that these genes could be considered beneficial markers for cancer diagnosis. However, researchers should conduct studies in future articles on whether these genes can be employed as biomarkers in gastrointestinal cancer.

In vitro and Pharmacoinformatics-based phytochemical screening for anticancer impacts of pistachio hull essential oil on AGS, PLC/PRF/5, and CACO2 cell lines.

The essential oil of pistacia vera (cv. Ohadi) hull (PHEO) was checked using gas chromatography mass spectrometry (GC/MS) analysis. It was studied the genes of the wnt pathway with a certain concentration of PHEO on Human gastric cancer (AGS), human hepatocellular carcinoma (PLC/PRF/5), and human colon cancer (CACO2) cell lines. After evaluating the survival rate of cancer cells by MTT test and determining IC50, pistachio hull essential oil (PHEO) was used for 24-hours to treat the cells. After RNA extraction, the expression of wnt pathway genes was evaluated by Real-Time PCR. Considering the crucial role of β-catenin accumulation and its effect on the progression of gastrointestinal cancers, Western blot analysis was also used to determine the effect of PHEO in protein expression of β-catenin inhibition. Also, an in silico analysis was carried out to investigate the effect of PHEO extracted compounds on protein expression of β-catenin and FZD7 inhibition. According to the results, wnt pathway genes were changed in samples treated using PHEO. The results showed the up-regulation of GSK-3β and down-regulation of Wnt-1, LEF-1, TCF1, and CTNNB1 genes compared to the control. We showed inhibition of β-catenin protein in cancer cell lines. Four compounds of PHEO were suggested to have an inhibition effect on β-catenin and FZD7. These compounds can be useful in the treatment of gastrointestinal cancers. Altogether, the inhibitory role of β-catenin protein can be very effective and can be considered one of the therapeutic goals in the treatment of gastrointestinal cancers.

Pleiotropic effects of DCLK1 in cancer and cancer stem cells.

Doublecortin-like kinase 1 (DCLK1), a protein molecule, has been identified as a tumor stem cell marker in the cancer cells of gastrointestinal, pancreas, and human colon. DCLK1 expression in cancers, such as breast carcinoma, lung carcinoma, hepatic cell carcinoma, tuft cells, and human cholangiocarcinoma, has shown a way to target the DCLK1 gene and downregulate its expression. Several studies have discussed the inhibition of tumor cell proliferation along with neoplastic cell arrest when the DCLK1 gene, which is expressed in both cancer and normal cells, was targeted successfully. In addition, previous studies have shown that DCLK1 plays a vital role in various cancer metastases. The correlation of DCLK1 with numerous stem cell receptors, signaling pathways, and genes suggests its direct or an indirect role in promoting tumorigenesis. Moreover, the impact of DCLK1 was found to be related to the functioning of an oncogene. The downregulation of DCLK1 expression by using targeted strategies, such as embracing the use of siRNA, miRNA, CRISPR/Cas9 technology, nanomolecules, specific monoclonal antibodies, and silencing the pathways regulated by DCLK1, has shown promising results in both in vitro and in vivo studies on gastrointestinal (GI) cancers. In this review, we will discuss about the present understanding of DCLK1 and its role in the progression of GI cancer and metastasis.

Regulatory Roles of Noncoding RNAs in the Progression of Gastrointestinal Cancers and Health Disparities.

Annually, more than a million individuals are diagnosed with gastrointestinal (GI) cancers worldwide. With the advancements in radio- and chemotherapy and surgery, the survival rates for GI cancer patients have improved in recent years. However, the prognosis for advanced-stage GI cancers remains poor. Site-specific GI cancers share a few common risk factors; however, they are largely distinct in their etiologies and descriptive epidemiologic profiles. A large number of mutations or copy number changes associated with carcinogenesis are commonly found in noncoding DNA regions, which transcribe several noncoding RNAs (ncRNAs) that are implicated to regulate cancer initiation, metastasis, and drug resistance. In this review, we summarize the regulatory functions of ncRNAs in GI cancer development, progression, chemoresistance, and health disparities. We also highlight the potential roles of ncRNAs as therapeutic targets and biomarkers, mainly focusing on their ethnicity-/race-specific prognostic value, and discuss the prospects of genome-wide association studies (GWAS) to investigate the contribution of ncRNAs in GI tumorigenesis.

Molecular Regulatory Roles of Long Non-coding RNA HOTTIP: An Overview in Gastrointestinal Cancers.

Gastrointestinal (GI) cancers presented an alarmingly high number of new cancer cases worldwide and are highly characterised by poor prognosis. The poor overall survival is mainly due to late detection and emerging challenges in treatment, particularly chemoresistance. Thus, the identification of novel molecular targets in GI cancer is highly regarded as the main focus. Recently, long non-coding RNAs (lncRNAs) have been discovered as potential novel molecular targets for combating cancer, as they are highly associated with carcinogenesis and have a great impact on cancer progression. Amongst lncRNAs, HOTTIP has demonstrated a prominent oncogenic regulation in cancer progression, particularly in GI cancers, including oesophageal cancer, gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. This review aimed to present a focused update on the regulatory roles of HOTTIP in GI cancer progression and chemoresistance, as well as deciphering the associated molecular mechanisms underlying their impact on cancer phenotypes and chemoresistance and the key molecules involved. It has been reported that it regulates the expression of various genes and proteins in GI cancers that impact cellular functions, including proliferation, adhesion, migration and invasion, apoptosis, chemosensitivity, and tumour differentiation. Furthermore, HOTTIP was also discovered to have a higher diagnostic value as compared to existing diagnostic biomarkers. Overall, HOTTIP has presented itself as a novel therapeutic target and potential diagnostic biomarker in the development of GI cancer treatment.

The Involvement of Human Papilloma Virus in Gastrointestinal Cancers.

Simple SummaryMounting evidence suggests a relationship between Human Papilloma Virus (HPV) infection and the occurrence of neoplastic transformations within oral, pharyngeal, and anal cancers. Other segments of the intestinal tract can also be involved. Knowledge about the association between HPV infection and gastrointestinal carcinogenesis is crucial for both cancer prevention and patient care. Unfortunately, definite conclusions cannot be drawn yet, due to the high number of contradictions in the published papers.Human Papilloma Virus (HPV) is one of the most common sexually transmitted infections worldwide. HPV infection has a strong relationship with the onset of cervix uteri, vagina, penis, anus, and oropharynx, but also tonsils and tongue cancers. Some epidemiological data indicate that except for gynecologic cancers, HPV infection can be one of the risk factors associated with a greater risk of induction and progression of gastrointestinal cancers. Data, however, remain contradictory and definite conclusions cannot be drawn, so far. The following review aims to organize recent evidence and summarize the current state of knowledge regarding the association between HPV infection and gastrointestinal tumors primarily focusing on esophageal, liver, gastric, colorectal, and anal cancers.

The Effects of CD73 on Gastrointestinal Cancer Progression and Treatment.

Gastrointestinal (GI) cancer is a common and deadly malignant tumor. CD73, a cell-surface protein, acts as a switch of the adenosine-related signaling pathway that can cause significant immunosuppression. Recent evidence has emerged that CD73 is a promising immunotherapy target for regaining immune cell function and restraining tumorigenesis, and a growing stream of research indicates that combining immunotherapy with other therapies can effectively improve the prognosis and survival of GI cancer patients. Several immune checkpoint inhibitors have been approved for use in GI cancer recently; however, they have demonstrated limited efficacy. Solving the problem of immunosuppression in GI cancer is the key to developing an effective therapeutic option and the modulation of CD73 expression may provide an answer. In this review, we discuss current research on CD73 in gastric, liver, pancreatic, and colorectal cancer to evaluate its therapeutic potential as an immunotherapy target in GI cancers.

Role of Prostaglandin E2 in the Progression of Gastrointestinal Cancer.

Chronic inflammation is a well-established risk factor for several diseases, including cancer. It influences tumor cell biology and the type and density of immune cells in the tumor microenvironment (TME), promoting cancer development. While proinflammatory cytokines and chemokines modulate cancer development, emerging evidence has shown that prostaglandin E2 (PGE2) is a known mediator connecting chronic inflammation to cancerization. This review highlights recent advances in our understanding of how the elevation of PGE2 production promotes gastrointestinal cancer initiation, progression, invasion, metastasis, and recurrence, including modulation of immune checkpoint signaling and the type and density of immune cells in the tumor/tissue microenvironment.

Fusobacterium nucleatum promotes esophageal squamous cell carcinoma progression via the NOD1/RIPK2/NF-κB pathway

Fusobacterium nucleatum, found in the oral cavity, influences the progression of gastrointestinal cancers. Additionally, our previous results suggested that F. nucleatum is associated with poor patient prognosis in esophageal squamous cell carcinoma (ESCC). However, the mechanism by which F. nucleatum affects aggressive tumor behavior has yet to be elucidated.We have conducted this clinical, in vitro, and in vivo study to clarify the mechanism of ESCC progression induced by F. nucleatum.Transmission electron microscopy revealed that F. nucleatum invaded and occupied ESCC cells and impacted gene and protein expression. Comprehensive mRNA expression and pathway enrichment analyses of F. nucleatum-treated ESCC cells identified the “NF-κB” and “NOD-like receptor” signaling pathways as enriched. We confirmed the relationship between the presence of F. nucleatum and NF-κB activation in resected ESCC tissues. Furthermore, F. nucleatum-treated ESCC cells demonstrated enhanced growth ability, and NF-κB activation, as well as overexpression of NOD1 and phosphorylated RIPK2. Furthermore, treated cells showed accelerated tumor growth, with NF-κB activation in xenograft models.F. nucleatum invaded ESCC cells and induced the NF-κB pathway through the NOD1/RIPK2 pathway, leading to tumor progression.

Cyclin-Dependent Kinase 4/6 Inhibitors: A Potential Breakthrough Therapy for Malignancies of Gastrointestinal Tract

Cancer is the leading cause of death worldwide for which effective treatments remain limited. This article aimed to critically review and discuss the potential of targeting cell cycle machineries as a vital tool for cancer treatment. Cyclin dependent kinase (CDK) 4/6 inhibitors were originally approved by the United State Food and Drug Administration (US FDA) for advanced-stage breast cancer treatment. The nearly double-prolonged survival time in patients who received CDK4/6 inhibitors are superior to the conventional chemotherapy or endocrine therapy alone and, thus, these medications have been designated a breakthrough therapy by the US FDA. The requirement of CDK4/6 in the progression of cancer cells, but probably dispensable in normal cells, makes CDK4/6 a popular target for cancer treatment. The effects of CDK4/6 inhibitors in cancer may also involve the tumor microenvironment in which the therapeutic effects are synergistically pronounced. These emerging roles, hence, prompt investigations regarding their therapeutic potential in other cancers, including gastrointestinal cancer. Many preclinical and clinical studies of CDK4/6 inhibitors in gastrointestinal cancers are underway and, as a result, several new potentials are gradually reported. Contrariwise, the primary effect of this drug group is arresting the cell cycle rather than inducing cell death. The efficacy of using CDK4/6 inhibitors as a single regimen in clinical practice is then limited. In this article, the effects of CDK4/6 inhibitors on the progression of gastrointestinal cancers, at both preclinical and clinical levels are reviewed. The future directions for research and the possibility of CDK4/6 inhibitors being "breakthrough therapy" for gastrointestinal cancers are also discussed.

Roles of Integrins in Gastrointestinal Cancer Metastasis.

Integrins are a large family of heterodimeric transmembrane receptors which mediate cell adhesion and transmit signals to the cell interior. The mechanistic roles of integrins have long been an enigma in cancer, given its complexity in regulating different cellular behaviors. Recently, however, increasing research is providing new insights into its function and the underlying mechanisms, which collectively include the influences of altered integrin expression on the aberrant signaling pathways and cancer progression. Many studies have also demonstrated the potentiality of integrins as therapeutic targets in cancer treatment. In this review, we have summarized these recent reports and put a particular emphasis on the dysregulated expression of integrins and how they regulate related signaling pathways to facilitate the metastatic progression of gastrointestinal cancer, including gastric cancer (GC) and colorectal cancer (CRC), which will address the crucial roles of integrins in gastrointestinal cancer.

The use of metformin in the treatment of gastrointestinal cancer

Type 2 diabetes mellitus and malignancies have several common risk factors, such as obesity, metabolic syndrome, hyperinsulinemia, and chronic inflammation. Currently these factors are considered as possible mechanisms that increase the risk of the development of malignanttumors, including gastrointestinal cancer. Epidemiological studies and meta-analyses indicate that patients with diabetes have a higher incidence and mortality from malignancies. Metformin is well-known oral hypoglycemic drug that belongs to the biguanide class and is being used to treat diabetes mellitus for almost a century. It has been established that in patients with diabetes mellitus, long-term use of metformin reduces the incidence of tumors and mortality from various cancers. The results of recent studies suggest that metformin may have direct pleiotropic anticancer activity against many tumor cells and their microenvironment. Its potential mechanisms include both insulin-dependent and insulin-independent. Moreover, metformin promotes antitumor immunosuppressive metabolic control of T lymphocytes and cancer cells, it is able to modulate the intestinal microbiota and renders a systemic effect on a body metabolism. The article presents data that reveal possible mechanisms of anticancer action of metformin and justify the use of metformin as a drug that may be useful for the treatment of gastrointestinal cancer. Although most of the clinical trials have retrospective design, they are often limited in time and patient bias, recent data from preclinical studies on the antitumor effects of metformin suggest that its effects on carcinogenesis and gastrointestinal cancer progression need to be further investigated. Future studies should consider the diabetic status, prognostic biomarkers, disease stage, and treatment regimens. Given that metformin is a safe and widely available drug with low cost, the feasibility of further study of its anti-cancer effects is beyond doubt.

Playing on the Dark Side: SMYD3 Acts as a Cancer Genome Keeper in Gastrointestinal Malignancies.

Simple SummaryThe activity of SMYD3 in promoting carcinogenesis is currently under debate. Growing evidence seems to confirm that SMYD3 overexpression correlates with poor prognosis, cancer growth and invasion, especially in gastrointestinal tumors. In this review, we dissect the emerging role played by SMYD3 in the regulation of cell cycle and DNA damage response by promoting homologous recombination (HR) repair and hence cancer cell genomic stability. Considering the crucial role of PARP1 in other DNA repair mechanisms, we also discuss a recently evaluated synthetic lethality approach based on the combined use of SMYD3 and PARP inhibitors. Interestingly, a significant proportion of HR-proficient gastrointestinal tumors expressing high levels of SMYD3 from the PanCanAtlas dataset seem to be eligible for this innovative strategy. This promising approach could be taken advantage of for therapeutic applications of SMYD3 inhibitors in cancer treatment.The SMYD3 methyltransferase has been found overexpressed in several types of cancers of the gastrointestinal (GI) tract. While high levels of SMYD3 have been positively correlated with cancer progression in cellular and advanced mice models, suggesting it as a potential risk and prognosis factor, its activity seems dispensable for autonomous in vitro cancer cell proliferation. Here, we present an in-depth analysis of SMYD3 functional role in the regulation of GI cancer progression. We first describe the oncogenic activity of SMYD3 as a transcriptional activator of genes involved in tumorigenesis, cancer development and transformation and as a co-regulator of key cancer-related pathways. Then, we dissect its role in orchestrating cell cycle regulation and DNA damage response (DDR) to genotoxic stress by promoting homologous recombination (HR) repair, thereby sustaining cancer cell genomic stability and tumor progression. Based on this evidence and on the involvement of PARP1 in other DDR mechanisms, we also outline a synthetic lethality approach consisting of the combined use of SMYD3 and PARP inhibitors, which recently showed promising therapeutic potential in HR-proficient GI tumors expressing high levels of SMYD3. Overall, these findings identify SMYD3 as a promising target for drug discovery.

Metabolism-associated genes in occurrence and development of gastrointestinal cancer: Latest progress and future prospect.

Gastrointestinal (GI) cancer remains one of the most prevalent cancers in the world. The occurrence and progression of GI cancer involve multiple events. Metabolic reprogramming is one of the hallmarks of cancer and is intricately related to tumorigenesis. Many metabolic genes are involved in the occurrence and development of GI cancer. Research approaches combining tumor genomics and metabolomics are more likely to provide deeper insights into this field. In this paper, we review the roles of metabolism-associated genes, especially those involved in the regulation pathways, in the occurrence and progression of GI cancer. We provide the latest progress and future prospect into the different molecular mechanisms of metabolism-associated genes involved in the occurrence and development of GI cancer.

Global Analysis of Microbiota Signatures in Four Major Types of Gastrointestinal Cancer.

The gut microbiota has been previously linked with tumorigenesis and gastrointestinal cancer progression; however, intra-tumor microbiota analysis has just emerged and deserves increasing attention. Based on the public databases of The Cancer Microbiome Atlas (TCMA) and The Cancer Genome Atlas (TCGA), this study identified the tissue/organ microbial signatures generated from 443 biosamples of four major gastrointestinal cancer types, including esophageal carcinoma (ESCA), which further includes esophageal adenocarcinoma (EAD) and esophageal squamous cell carcinoma (ESCC), stomach adenocarcinoma (STAD), colon adenocarcinoma (COAD), and rectum adenocarcinoma (READ). According to partial least squares discrimination analysis (PLS-DA), the profile differences in microbial communities between the tumor and normal samples were not particularly noticeable across the four cancer cohorts, whereas paired comparison analyses revealed several specific differences in bacteria between tumor and normal samples in the EAD, STAD, and COAD samples. The taxa classified from the phylum to genus level revealed a trend of distinguishable microbial profiles between upper and lower gastrointestinal tumors. The Bacteroidetes/Firmicutes ratio in lower gastrointestinal tract tumors was nearly three times that in upper gastrointestinal tract tumors. We also determined the relative tissue/organ-prevalent microbes for each of the four cohorts at the order and genus levels. Microbe Alistipes, Blautia, Pasteurellales, and Porphyromonas compositions were correlated with the clinical characteristics of patients with gastrointestinal cancer, particularly colorectal cancer. Taken together, our findings indicate that microbial profiles shift across different gastrointestinal cancer types and that microbial colonization is highly site-specific. Composition of specific microbes can be indicative of cancer stage or disease progression. Overall, this study indicates that the microbial community and abundance in human tissues can be determined using publicly available data, and provides a new perspective for intra-tissue/organ microbiota research.

Prognostic value of low microRNA-34a expression in human gastrointestinal cancer: a systematic review and meta-analysis

BackgroundMounting evidence shows that microRNA-34a (miR-34a) is involved in cancer prognosis. Therefore, we summarize the predictive role of miR-34a for survival in patients with gastrointestinal cancers (GICs).MethodsAll eligible studies were found by searching PubMed, Web of Science and EMBASE, and survival results were extracted. Then, the hazard ratio (HR) with the corresponding 95% confidence interval (CI) was calculated to evaluate the prognostic role of miR-34a in GICs. The association between miR-34a expression and clinicopathological characteristics was estimated by odds ratios (ORs) and 95% CIs.ResultsA total of 20 studies were included in this meta-analysis. For overall survival (OS), lower miR-34a expression could probably predict poorer outcome in GICs, with a pooled HR of 1.86 (95% CI: 1.52–2.28, P < 0.01). For disease-free survival (DFS), progression-free survival (PFS), and recurrence-free survival (RFS), lower miR-34a expression was related to worse DFS/PFS/RFS with a pooled HR of 1.86 (95% CI: 1.31–2.63, P < 0.01). A significant relation of differentiation/TNM stage/lymphatic metastasis and the expression level of miR-34a was identified.ConclusionThis meta-analysis revealed that lower miR-34a expression is significantly connected with worse OS and DFS/PFS/RFS in GIC patients. In addition, the miR-34a expression level is relatively lower in patients with lymph node metastasis than in patients without lymph node metastasis, and decreased miR-34a expression levels are linked to poor tumour differentiation and late TNM stage. MiR-34a may become a new factor for the prognosis prediction and progression of GICs.

Autophagy and gastrointestinal cancers: the behind the scenes role of long non-coding RNAs in initiation, progression, and treatment resistance.

Gastrointestinal (GI) cancers comprise a heterogeneous group of complex disorders that affect different organs, including esophagus, stomach, gallbladder, liver, biliary tract, pancreas, small intestine, colon, rectum, and anus. Recently, an explosion in nucleic acid-based technologies has led to the discovery of long non-coding RNAs (lncRNAs) that have been found to possess unique regulatory functions. This class of RNAs is >200 nucleotides in length, and is characterized by their lack of protein coding. LncRNAs exert regulatory effects in GI cancer development by affecting different functions such as the proliferation and metastasis of cancer cells, apoptosis, glycolysis and angiogenesis. Over the past few decades, considerable evidence has revealed the important role of autophagy in both GI cancer progression and suppression. In addition, recent studies have confirmed a significant correlation between lncRNAs and the regulation of autophagy. In this review, we summarize how lncRNAs play a behind the scenes role in the pathogenesis of GI cancers through regulation of autophagy.