Smoking is the leading cause of cancer, and smokers are at a higher risk of developing digestive system disorders, including digestive tract cancers (23,24). In 2019, tobacco smoking was responsible for ~203,000 deaths of patients with EC worldwide (25). Increasing evidence has demonstrated that smoking is closely associated with the development and progression of HCC, with 13% of HCC cases reported to be caused by smoking worldwide (26,27). In a statistical analysis of HCC, patients were categorized as non-smokers, current smokers and ex-smokers, according to smoking status; notably, non-smokers had higher late survival rates than current smokers and ex-smokers (28). For PC, tobacco smoking is considered a major risk factor, with former or current smokers exhibiting a higher odds ratio of 1.42–1.74 than non-smokers (24,29). A number of causative factors have been epidemiologically confirmed to have an association with PC, among which smoking shows the most positive correlation with the risk of PC and is a recognized risk factor (30–33). Furthermore, smoking has been shown to affect the prognosis of patients with PC (34). Similarly, smoking constitutes an established risk factor for CRC. Compared with 6,866 healthy individuals, 6,264 patients with CRC had a higher smoking status, suggesting a strong association between smoking and CRC evident across early- and late-stage CRC (35).

Notably, research in esophageal squamous cell carcinoma (ESCC), bladder cancer, non-small lung cancer and CRC has demonstrated that there is no correlation between SNHG16 expression and smoking (20,36–38). Specifically, in lung cancer, SNHG16 expression was not related to the clinical data of patients, including age and smoking history (39). Furthermore, a meta-analysis study indicated that SNHG16 expression was not associated with smoking (40). By contrast, in a study on CRC, Zhou et al revealed that smoking influenced the combination of rs7353, rs8038 and rs15278 sites located in the SNHG16 gene. In addition, through multifactor dimensionality reduction analysis, changes in the expression levels of SNHG16 were revealed to increase or decrease the risk of CRC susceptibility (41). In the future, the association between smoking and SNHG16 expression in other types of cancer requires further research.

Similar to smoking, excessive alcohol consumption is associated with an increased risk of all digestive system tumors, including EC (24,42), HCC (43), PC (44), GC (45) and CRC (46). Nevertheless, moderate alcohol consumption has shown no association with certain types of digestive cancer, such as HCC, PC, GC and CRC (24,47,48). An Australian study revealed that the risk of ESCC was significantly increased with combined tobacco and alcohol use, surpassing >20-fold higher risk compared with non-smokers and non-drinkers (49).

In addition to smoking, Zhou et al (41) also revealed that drinking was a factor affecting SNHG16 single nucleotide polymorphisms and expression, thus affecting CRC susceptibility. To the best of our knowledge, the association between excessive alcohol consumption and SNHG16 expression has not been reported in other diseases.

Physical activity involves the use of skeletal muscles and requires energy expenditure. Numerous studies have demonstrated the association between physical activity and cancers (50–53). Physical activity can decrease the risk of EC by 19–51%, GC by 15–19% and colon cancer by 21–27% (50). In particular, high levels of physical activity, such as running and jumping rope, may decrease the risk of PC by 9–25% (50). Moore et al reported that high levels of physical activity decreased the risk of EC, HCC and GC by >20% (51). Kasvis and Kilgour (53) suggested that physical activity interventions may alleviate malnutrition and muscle wasting, which are common in PC. In China, a decade-long prospective study showed that CRC risk was 25% lower in the highest-level-of-activity group compared with in the lowest-level-of-activity group (52). In addition, a meta-analysis showed that a moderate-to-high physical activity level serves as a common protective factor that can significantly reduce the overall risk of digestive system cancer (54). To date, there is an absence of evidence to indicate the relationship between physical activity and SNHG16 expression, which should be explored in the future.

Evidence has suggested that bacterial infection serves a key role in tumor progression, such as in EC (55). Porphyromonas gingivalis is an important periodontal disease pathogen that has been detected in 61% of ESCC tissues (56). It has been suggested that EC is moderately positively associated with chronic hepatitis C virus (HCV) infection, with a combined relative risk of 1.61 (95% CI, 1.19–2.17) (57). For HCC, the most common risk factor is chronic hepatitis caused by hepatitis B virus (HBV) and HCV infection, and long-term chronic hepatitis can lead to cirrhosis and eventually develop into HCC (58). Furthermore, HBV products and HBV mutations may disrupt normal cell signaling pathways, leading to HBV-induced HCC (59). Fusobacterium has been identified as a potential prognostic biomarker for PC (60). A prospective study reported that patients with high concentrations of P. gingivalis have a higher risk of PC (61). Helicobacter pylori, which is found only in the human stomach, has been shown to be closely associated with GC as a separate risk factor (62,63). Substantial evidence has suggested that H. pylori carrying CagA and VacA virulence factors is highly associated with distal GC by promoting GC epithelial-mesenchymal transition (EMT) through disruption of the gastric tissue microenvironment (64–67). The Epstein-Barr virus infection can also cause GC, accounting for ~10% of patients with GC (68). In patients with CRC, Escherichia coli has been reported to contain a polyketide synthase gene that not only induces inflammation, epithelial cell damage and cell proliferation, but also encodes colibactin, which destroys DNA and ultimately leads to the formation of CRC (69). Fusobacterium has also been reported to be associated with the occurrence of CRC (70).

In some clinical samples of HCC, HBV infection showed no correlation with the expression of SNHG16 (71–75). In addition, in a meta-analysis by Liu et al, there was no association detected between SNHG16 expression and HBV infection (76). To the best of our knowledge, in other human digestive system tumors, the association between infection and SNHG16 expression has not been reported. In some cells, SNHG16 expression was upregulated in Cryptococcus-treated dendritic cells compared with in wild-type dendritic cells (77). In addition, Mycobacterium tuberculosis infection can increase the expression levels of SNHG16 in a dose- and time-dependent manner in macrophages (78).

Radiation is a common tool in modern medicine, including ionizing radiation and radiotherapy, and is one of the main treatments for cancer (79–81). However, the disadvantages of radiation cannot be overlooked. In patients with head and neck tumors, the risk of ESCC is associated with the dose of radiotherapy (80). In addition, α-radiation emitted by plutonium is strongly associated with genetic mutations in HCC (82). Dores et al (83) proposed that both radiotherapy and chemotherapy can substantially increase the risk of PC in Hodgkin lymphoma survivors treated previously. In addition, Yusefi et al (84) showed that ionizing radiation is a possible risk factor for GC. Low-dose radiation exposure among uranium miners has been reported to be positively associated with GC (85). Computerized tomography radiation slightly increases the risk of CRC, whereas the benefits of computerized tomography (CT) radiation far outweigh the risks (86). Notably, to the best of our knowledge, the association between radiation and SNHG16 expression has not been reported in disease.

A study in China revealed that drinking from untreated water sources can increase the risk of ESCC by 2-fold (87). The use of polluted water containing nitrate is considered an essential risk factor for HCC (88), PC (89), GC (90) and CRC (91). Exposure to external airborne agents, such as fine particulate matter, may also increase the risk of digestive system cancer, especially EC and GC (92,93). Tsai et al (93) demonstrated that PM2.5 was strongly associated with the mortality of HCC, which agrees with the results of another study, where a strong association was detected between PM2.5 and HCC and CRC (94). A previous study reported that SNHG16 expression presented no significant differences between Intensive Care Unit (ICU)-hospitalized and non-ICU hospitalized patients (95). To the best of our knowledge, in digestive system cancer, the effect of living environment on SNHG16 expression is not known.

A number of studies have shown that a family history of cancer is strongly associated with the incidence rate of certain types of cancer, such as EC (96), HCC (97), PC (98), GC (99) and CRC (100). Parents and siblings of a person with EC and HCC have been reported to exhibit a higher risk of developing EC and HCC. Research has found that there is a clear ‘dose-response’ relationship with the number of first-degree relatives of EC (97,101). Furthermore, familial inheritance is a known cause of GC (102). A positive first-degree family history of CRC and GC can reduce the risk of cancer recurrence and death compared with patients without a family history, based on a well-defined cohort enrolled in a clinical trial (103,104). Su et al (105) reported that people with a family history of EC had a 2-fold higher risk of developing the disease with a poorer prognosis. However, in another study, the HCC survival rate was higher in the familial cancer group than in the sporadic cancer group (106). Furthermore, individuals with a family history of CRC have been shown to have a slightly increased risk of getting PC (107).

In a study on CRC, Zhou et al indicated that family history affected the combination of rs7353, rs8038 and rs15278 sites of the SNHG16 gene, which increased or decreased SNHG16 expression and influenced CRC susceptibility (41). Whereas in other diseases, this relationship has not been presented.

There is a consensus on the strong association between diet and digestive system tumors. Long-term unbalanced diets, such as high-calorie hot beverages or food, can lead to esophageal epithelial cell damage and exacerbate the risk of EC (108). A number of studies have demonstrated that reducing vegetable and fruit intake, and low-fiber diets, may increase the risk of HCC and PC, and increasing the intake of salted and preserved foods and meat could increase the risk of HCC and GC (109–114). Similarly, diet also influences CRC. For example, calcium, fiber, milk, wholegrains and 2′5-hydroxyvitamin D have been shown to inhibit the development of CRC; however, consumption of a large amount of red or culinary meat can increase the risk of CRC (115,116). Furthermore, patients with CRC have been reported to be deficient in vitamin C, vitamin E and folate (117). To the best of our knowledge, the association between diet and SNHG16 expression has not been published.

Existing studies have shown that both infectious diseases and chronic inflammation may account for ~25% of carcinogenic factors (118). Reactive oxygen/nitrogen species are produced under the condition of chronic inflammation, which can cause DNA damage in various organs, thereby inducing cellular carcinogenesis (118,119). Furthermore, prolonged acid reflux can cause reflux esophagitis in the proximal esophagus and expedite esophageal carcinogenesis (120). Non-alcoholic fatty liver disease can result in a series of diseases, including steatosis accumulation, non-alcoholic steatohepatitis, inflammation, liver fibrosis and cirrhosis, which may eventually lead to HCC (121–123). Chronic pancreatitis is also a causative factor in the development of PC. Patients who have had this disease for >2 years face a 2.71-fold higher risk of developing PC (124). Chronic gastritis, one of the most common types of chronic inflammation, is considered a precursor of GC (125,126). Chronic enteritis and dysbiosis of the intestinal microflora can increase the risk of CRC (127). Notably, diabetes mellitus (DM) and obesity are risk factors for digestive system cancer, enhancing the development of EC (128), HCC (29), PC (129,130), GC (131,132) and CRC (133). For example, type 2 DM (T2DM) is often recognized as an independent risk factor for HCC, with a 2- to 4-fold increased risk in patients with T2DM compared with the general population (134).

In HCC, liver cirrhosis has been reported to not necessarily be associated with the expression of SNHG16 (71,74,75,135). By contrast, investigations into the association between portal vein tumor thrombus (PVTT) and SNHG16 expression have yielded dissimilar results. Guo et al (135) revealed a positive correlation between SNHG16 expression and PVTT, while another study indicated that high SNHG16 expression was independent of PVTT (136). Patients with sepsis and acute respiratory distress syndrome (ARDS) have been shown to exhibit a decline SNHG16 expression compared with those without ARDS, indicating that SNHG16 may possess a certain ability to discriminate patients with sepsis and ARDS from those without ARDS, according to the area under curve (137). Moreover, SNHG16 in patients with sepsis has been discovered to have a negative correlation with diabetes and chronic obstructive pulmonary disease history, rather than other medical history, such as hypertension (137). In addition, some studies have found that SNHG16 serves an important role in sepsis-induced acute lung injury and inflammation via an involvement in the pathogenesis of ARDS (138–140). In patients with acute ischemic stroke, SNHG16 expression was revealed to be negatively related to comorbidities, such as hyperlipidemia and disease severity (141). SNHG16 has been shown to be upregulated in unilateral ureteral obstruction-induced renal fibrotic tissues of mice (142).

Cancer is a multi-stage process disease and its occurrence is not only disturbed by external factors, but also by intrinsic genetic mutations. The occurrence of genetic mutations serves an important role in the development of digestive system tumors. KRAS, a proto-oncogene, affects the cellular proliferation and differentiation in digestive system cancer, and can influence the prognosis of these patients (143,144). KRAS mutations have been found in ~85% of patients with PC and ~45% of patients with CRC (145). Similar results have been reported regarding tumor suppressor genes. Mutations in the TP53 gene usually occur in the early stages of GC and can accelerate the progression of GC (146). In HCC, TP53 mutations have been detected in circulating exosomal DNA and are associated with the prognosis of patients (147). APC mutations are associated with tumorigenesis, affecting the overall survival of patients with CRC (148,149). A previous meta-analysis showed the neutral function of PIK3CA mutations on the overall survival and progression-free survival of patients with CRC (144). Specifically, individuals who have both genetic and lifestyle-related risks have a ~190 times higher risk of ESCC than those without these risks (150). To the best of our knowledge, the association between genomic characteristics and SNHG16 expression has not yet been presented.

Epigenetic influences, such as DNA methylation, histone modifications and non-coding RNA regulation, are also important factors (151). The role of lncRNA in the process of cancer development and progression cannot be overlooked. A number of studies have shown that SNHG16 is a key factor in the process of digestive system cancer, including promoting the proliferation of cancer cells, resisting cancer therapeutic drugs and enhancing cancer cell invasiveness. The possible mechanisms and functional characterization of SNHG16 in human digestive system cancer are presented in Fig. 1 and Table I, respectively. Furthermore, the association between SNHG16 expression and clinicopathological characteristics is summarized in Table II.

EC is one of the major cancer types worldwide, ranking 7th (3.1%, 604,100 new cases) and 6th (5.5%, 544, 076 deaths) among all types of cancer in terms of incidence and mortality rate, respectively (2). Its incidence and mortality rates vary between geographic regions (2). For example, due to economic underdevelopment and dietary habits, the burden of EC is higher in East Asia with a predominance of patients with ESCC (2). Studies have shown that SNHG16 expression is upregulated in EC, and is closely associated with tumor stage, lymph node metastasis and clinical stage (36,152–154). The knockdown of SNHG16 has been reported to suppress the proliferation and invasion, and promote apoptosis by reducing the expression of β-catenin, cyclin D1 and c-Myc protein in EC-1 and Eca-109 cells (36). In addition, Zhang et al verified by reverse transcription-quantitative PCR (RT-qPCR) that the expression levels of SNHG16 were upregulated in EC tissues or cells compared with those in normal tissues or cells (P<0.01). This previous study also observed that the disruption of SNHG16 expression suppressed proliferation, promoted apoptosis and inhibited EMT through the miR-140-5p/ZEB1 axis in vivo and in vitro (152). In another study on ESCC, the expression of SNHG16 was revealed to be associated with tumor differentiation and T stage, and increased expression of SNHG16 could promote ESCC growth and metastasis. The underlying mechanism may be that SNHG16 binds to and recruits EIF4A3 to modulate RhoU expression, thereby enhancing the stability of RhoU mRNA (154). Zhang et al (153) demonstrated that SNHG16 acts as a sponge of miR-802 to upregulate PTCH1 and activate the Hedgehog pathway, thus facilitating EC proliferation and self-renewal.

These results show that the upregulation of SNHG16 may be strongly associated with the development of ESCC, suggesting the potential utility of SNHG16 as a marker for ESCC. These insights offer novel avenues for the clinical management of ESCC.

HCC is one of the most common malignancies worldwide, accounting for 4.7% (906,000 new cases) of all new cancer cases and 8.3% (830,000 deaths) of all cancer-related mortalities. HCC is ranked as the 6th most commonly diagnosed cancer and the 3rd leading cause of cancer-related deaths (2). In most studies, SNHG16 has been considered a proto-oncogene of HCC, and RT-qPCR has been used to detect the expression of SNHG16 in HCC tissues and corresponding non-tumor tissues. The results showed that the expression levels of SNHG16 in HCC samples were much higher than those in matched non-tumor samples, and upregulation of SNHG16 expression was highly associated with poor prognosis and tumor stage of HCC. Furthermore, the patients with advanced-stage HCC exhibited a significantly higher SNHG16 expression level than the patients with early-stage HCC (72,155). Moreover, the high expression of SNHG16 has been shown to be associated with the tumor size, TNM stage and vascular infiltration of patients with HCC (74). SNHG16, as a ceRNA, can target STAT3 and GALNT1 through sponging miR-4500 in Huh7 cells and human umbilical vein endothelial cells (HUVECs), respectively, to promote proliferation, metastasis and invasion of Huh7 cells, and enhance angiogenesis of HUVECs (72,156). In addition, through regulating miR-195, miR-17-5p/P62, miR-302a-3p/FGF19 and miR-186 expression, SNHG16 can inhibit the proliferation, migration and invasion of HepG2 and Hep3B cells (71,73,155,157). Overexpression of SNHG16 may also affect the G₂/M transition of HCC cells by regulating CDC25B expression through sponging miR-let-7b-5p (158). A previous study reported that SNHG16 is upregulated in sorafenib-resistant tumor tissues and cells, and that the overexpression of SNHG16 can enhance sorafenib resistance in HCC (74). By contrast, when the expression of SNHG16 is suppressed, sorafenib resistance disappears (135). Jing et al (159) also suggested that SNHG16 may enhance HCC autophagy via the miR-23b-3p/EGR1 axis and protect HCC from sorafenib resistance. In addition, it has been reported that SNHG16 can be phagocytized by telocytes and can mediate telocytes to promote HCC cell metastasis by regulating the miR-942-3p/MMP9 axis (160). Furthermore, Hu et al (75) demonstrated that the overexpression of SNHG16 promotes TRAF6 expression by sponging miR-605-3p, activates NF-κB and exacerbates the development of HCC. Specifically, the activated NF-κB can enhance SNHG16 promoter activity, forming a positive SNHG16/NF-κB feedback loop that further worsens HCC (75). The overexpression of SNHG16 has also been shown to be associated with tumor recurrence and poor prognosis after surgery, and mechanistic analyses suggested that SNHG16 markedly activates the extracellular matrix-receptor interaction pathway (136).

Studies have demonstrated that SNHG16 regulates a large lncRNA-miRNA-mRNA network in HCC, and is closely associated with the infiltration of immune cells, the release of immunomodulatory factors and the expression of chemokines in tumor tissues (161–163). Notably, UBE4B and SEMA3F may promote HCC progression regulated by their upstream SNHG16/miR-22-3p and SNHG16/let-7c-5p axes, respectively (163,164). Liu et al (76) revealed that SNHG16 can be used as a potential biomarker for patients with HCC with a poor prognoses. In summary, SNHG16 may be upregulated in HCC and can promote HCC development. Notably, a previous study presented the opposite argument, suggesting that SNHG16 expression may be reduced in HCC tissue compared with in normal liver tissue, and that overexpression of SNHG16 could decrease the proliferation of Hep3B and Huh7 cells, and inhibit HCC development and chemoresistance via sponging miR-93 (165). This discrepancy in findings may stem from the diverse dysregulation patterns of SNHG16 in human cancer, with its expression being either upregulated or downregulated. Such variations could be influenced by the specific cancer types, their anatomical locations and the microenvironments involved (165). This discrepancy prompts further research into the role of SNHG16 in HCC.

PC is one of the most serious malignancies of the digestive system. Due to its poor prognosis, PC accounts for almost as many deaths (466,000) as cases (496,000) in the world, and is the 7th leading cause of cancer death in both men and women (2). Similar to EC, the incidence rate of PC is 4-fold and 5-fold higher in high human development index (HDI) countries compared with in low HDI countries (2). Studies have shown that the expression levels of SNHG16 are upregulated in PC tissue compared with those in normal tissue (166,167). Altering the expression of SNHG16 may inhibit the adipogenesis of AsPC-1 and PANC-1 cells through the miR-195/SREBP2 axis (168). Inhibition of SNHG16 expression can result in the release of miR-302b-3p, which inhibits SLC2A4 expression and promotes apoptosis in PC cells (166). Overexpression of SNHG16 has also been reported to be closely associated with gemcitabine resistance in PC cells. SNHG16 can interact with EZH2, suppressing SMAD4 expression via EZH2 binding to the SMAD4 promoter (167). Downregulation of SMAD4 has a reduced ability to inhibit AKT phosphorylation, thereby promoting gemcitabine resistance in PC cells (167). These findings suggested that SNHG16 may serve a critical role in the development of PC and that it could be regarded as a marker of poor prognosis in PC.

GC remains an important type of cancer worldwide, and is considered the 5th most frequent malignancy (5.6%, >1,000,000 new cases) and the 4th most common cause of death (7.7%, ~769,000 deaths) among oncological patients (2). The region with the highest age-standardized incidence rate is Eastern Asia, followed by Central and Eastern Europe (2). The expression of SNHG16 is significantly associated with the depth of infiltration, lymph node metastasis, TNM stage, histological differentiation and PTBP1 expression of GC (169,170). Knockdown of SNHG16 can significantly suppress the migration, invasion and arrest of cells in the G₁ phase, and can decrease c-Myc expression, and affect the formation of the p27/cyclin D1/CDK6, p53/cyclin E1 and cyclin A2/CDK2 complexes (169–171). A number of patients with GC develop 5-fluorouracil (5-FU) resistance, showing a higher vulnerability than parental GC cells. Notably, blocking the SNHG16/miR-506-3p/PTBP1 axis may effectively limit 5-FU-resistant GC cell originated-xenograft tumor growth under 5-FU treatment. Specifically, PTBP1 stabilizes the mRNA expression of glycolysis enzymes by directly binding to 3′UTR regions (169). In addition, it has been shown that SNHG16 can promote EMT by downregulating the WNT signaling pathway and inhibiting DKK3 expression, and can regulate β-catenin protein expression without participating in the β-catenin translocation between the cytoplasm and nucleus (172). In particular, SNHG16 activated by CCCTC binding factor (CTCF) can modulate gastrointestinal stromal tumor cell proliferation, migration, invasion and apoptosis through the miR-128-3p/CASC3 axis (173). In another study, SNHG16 was also demonstrated to be able to mediate the upregulation of JAK2 and STAT3 by sponging miR-135a to influence the proliferation, invasion and apoptosis of GC cells, with SNHG16 being regulated by phosphorylated-STAT3 directly or indirectly (174). In summary, SNHG16 may be closely related to the occurrence and development of GC, and could be a potential marker of poor GC prognosis.

Notably, >1,900,000 new cases of CRC and 935,000 CRC-related deaths occurred worldwide in 2020; during this year, it was the third most common cancer, after female breast cancer and lung cancer, and it exhibited a close mortality rate to lung cancer (2). Growing evidence has suggested that the expression levels of SNHG16 are positively associated with advanced TNM stage, distant metastasis and shorter overall survival time in CRC (38,175–177). SNHG16 is mainly present in the cytoplasm, functioning as a ceRNA to regulate multiple miRNAs and target genes. Li et al (38) revealed that SNHG16 was associated with malignancy and poor prognosis in patients with CRC by sponging miR-200a-3p. Tan et al (177) indicated that SNHG16 could promote CRC proliferation by upregulating its target gene ABCB1 through interacting with miR-214-3p. He et al (178) concluded that SNHG16 could activate USP22 expression to promote CRC progression via absorbing miR-132-3p. Ke et al (179) demonstrated that SNHG16 supported colon cancer cell proliferation by targeting the miR-302a-3p/AKT axis. Chen et al (176) revealed that the expression of SNHG16 was higher in cancer tissues from patients than in the matched normal tissues, and was positively related to CRC grade. It was also revealed that SNHG16 may serve a contributory role in the proliferation, migration and EMT of CRC cells through the miR-124-3p/MCP-1 axis (176). Some bioinformatics analyses also reached a similar conclusion, in that SNHG16 may have an important role in CRC (175,180). In particular, SNHG16 has been reported to be closely associated with autophagy in CRC (175,181).

The expression of SNHG16 may be activated by other proteins, such as c-Myc. Christensen et al reported that the expression of SNHG16 is determined by Wnt-regulated transcription factors such as c-Myc in CRC (182). Specifically, knockdown of β-catenin could reduce the expression of SNHG16 and c-Myc, whereas c-Myc knockdown or overexpression could decrease or increase the SNHG16 expression, respectively (182). In a study by Xiang et al, the SNHG16/YAP1/TEA domain transcription factor 1 (TEAD1) positive feedback loop was detected in CRC cells (183). SNHG16 was shown to act as a ceRNA that can physically bind miR-195-5p, further regulating YAP1 expression and facilitating tumor progression. YAP1 binds to TEAD1 to form a YAP1/TEAD1 complex, which in turn binds to two sites in the promoter of SNHG16 and activates SNHG16 transcription (183).

In addition, SNHG16 polymorphisms have been shown to be significantly associated with CRC susceptibility. Research has revealed that the rs7353 site A>G of the SNHG16 gene is associated with decreased susceptibility of CRC; however, the rs8038 site G>A, rs15278 site A>G and rs15278 site G>A variations may increase CRC susceptibility (41).

SNHG16 has also been studied in other gastrointestinal tumors. For example, SNHG16 expression has been shown to be upregulated in cholangiocarcinoma tissues and cell lines. When SNHG16 expression was suppressed, the proliferation rate of RBE and HuCCT1 cells was reduced, whereas apoptosis was activated (184). Wu et al (184) also revealed that there was a potential binding site for miR-146a-5p at the 3′UTR end of GATA6 and that SNHG16 could sponge miR-146a-5p. Interfering with the expression of miR-146a-5p reversed the SNHG16 knockdown-induced apoptosis in RBE and HuCCT1 cells, whereas overexpression of GATA6 also achieved the same effect (184). These findings suggested that SNHG16 is important for the development of cholangiocarcinoma and it could be a potential target for future drug development against cholangiocarcinoma.

Neuroendocrine tumors account for a very small portion of tumors at each site; for example, the incidence of pancreatic neuroendocrine tumors was <1 case per 100,000 people/year worldwide (1), and the incidence of gastric neuroendocrine tumors was ~0.4 per 100,000 individuals in America in 2017 (185). However, as the number of patients with cancer increases, the proportion of neuroendocrine tumors has also increased, thus highlighting the need for attention to be paid to neuroendocrine tumors. Although, to the best of our knowledge, the role of SNHG16 in neuroendocrine tumors in the digestive system has not been reported, it is a valuable direction for improving the management of neuroendocrine tumors in the future.