SLC26A9 promotes colorectal tumorigenesis by modulating Wnt/ß-catenin signaling.

Solute carrier family 26 member 9 (SLC26A9) is a member of the Slc26a family of multifunctional anion transporters that functions as a Cl- channel in parietal cells during acid secretion. We explored the role of SLC26A9 in colorectal cancer (CRC) and its related mechanisms through clinical samples from CRC patients, CRC cell lines and mouse models. We observed that SLC26A9 was expressed at low levels in the cytoplasm of adjacent tissues, polyps and adenomas but was significantly increased in colorectal adenocarcinoma. Moreover, increased levels of SLC26A9 were associated with a high risk of disease and poor prognosis. In addition, downregulation of SLC26A9 in CRC cells induced cell cycle arrest and apoptosis but inhibited cell proliferation and xenograft tumor growth both in vitro and in vivo. Mechanistic analysis revealed that SLC26A9 was colocalized with ß-catenin in the nucleus of CRC cells. The translocation of these two proteins from the cytoplasm to the nucleus reflected the activation of Wnt/ß-catenin signaling, and promoted the transcription of downstream target proteins, including CyclinD1, c-Myc and Snail, but inhibited the expression of cytochrome C (Cyt-c), cleaved Caspase9, cleaved Caspase3 and apoptosis-inducing factor (AIF). CRC is accompanied by alteration of epithelial mesenchymal transition (EMT) markers. Meanwhile, further studies showed that in SW48 cells, overexpressing SLC26A9 was cocultured with the ß-catenin inhibitor XAV-939, ß-catenin was downregulated, and EMT was reversed. Our study demonstrated SLC26A9 may be responsible for alterations in the proliferative ability and aggressive potential of CRC by regulating the Wnt/ß-catenin signaling pathway.

The S100 calcium-binding protein A6 plays a crucial role in hepatic steatosis by mediating lipophagy.

BACKGROUND: S100 calcium-binding protein A6 (S100A6) is a calcium-binding protein that is involved in a variety of cellular processes, such as proliferation, apoptosis, and the cellular response to various stress stimuli. However, its role in NAFLD and associated metabolic diseases remains uncertain. METHODS AND RESULTS: In this study, we revealed a new function and mechanism of S100A6 in NAFLD. S100A6 expression was upregulated in human and mouse livers with hepatic steatosis, and the depletion of hepatic S100A6 remarkably inhibited lipid accumulation, insulin resistance, inflammation, and obesity in a high-fat, high-cholesterol (HFHC) diet-induced murine hepatic steatosis model. In vitro mechanistic investigations showed that the depletion of S100A6 in hepatocytes restored lipophagy, suggesting S100A6 inhibition could alleviate HFHC-induced NAFLD. Moreover, S100A6 liver-specific ablation mediated by AAV9 alleviated NAFLD in obese mice. CONCLUSIONS: Our study demonstrates that S100A6 functions as a positive regulator of NAFLD, targeting the S100A6-lipophagy axis may be a promising treatment option for NAFLD and associated metabolic diseases.

A potential tumor marker: Chaperonin containing TCP­1 controls the development of malignant tumors (Review).

Due to concealment, high invasiveness and a lack of indicators, malignant tumors have emerged as one of the deadliest diseases worldwide and their incidence is rising yearly. Research has revealed that the chaperonin family member, chaperonin containing TCP­1 (CCT), serves a crucial role in malignant tumors. CCT is involved in the growth of numerous malignant tumors such as lung cancer, breast cancer, hepatocellular carcinoma and colorectal cancer and assists the folding of a number of proteins linked to cancer, such as KRAS, p53 and STAT3. According to clinical data, CCT is highly expressed in a range of tumor cells and is associated with poor patient prognosis. In addition, through controlling the cell cycle or interacting with other proteins (including YAP1, HoXB2 and SMAD2), CCT has an effect on the proliferation, invasion and migration of cancer cells. As a result, it is possible that CCT will become a new tumor marker or therapeutic target, which will provide some guidance for early tumor screening or late tumor prognosis. In the present review, the molecular properties of CCT are introduced, alongside a summary of its interactions with other cancer­related proteins and a discussion of its function in common malignant tumors. It is expected that the present review will offer fresh approaches to the treatment of cancer.

Novel roles of karyopherin subunit alpha 2 in hepatocellular carcinoma.

Hepatocellular carcinoma is the most common type of liver cancer and associated with a high fatality rate. This disease poses a major threat to human health worldwide. A considerable number of genetic and epigenetic factors are involved in the development of hepatocellular carcinoma. However, the molecular mechanism underlying the progression of hepatocellular carcinoma remains unclear. Karyopherin subunit alpha 2 (KPNA2), also termed importin α1, is a member of the nuclear transporter family. In recent years, KPNA2 has been gradually linked to the nuclear transport pathway for a variety of tumor-associated proteins. Furthermore, it promotes tumor development by participating in various pathophysiological processes such as cell proliferation, apoptosis, immune response, and viral infection. In hepatocellular carcinoma, it has been found that KPNA2 expression is significantly higher in liver cancer tissues versus paracancerous tissues. Moreover, it has been identified as a marker of poor prognosis and early recurrence in patients with hepatocellular carcinoma. Nevertheless, the role of KPNA2 in the development of hepatocellular carcinoma remains to be determined. This review summarizes the current knowledge on the pathogenesis and role of KPNA2 in hepatocellular carcinoma, and provides new directions and strategies for the diagnosis, treatment, and prediction of prognosis of this disease.

Digestive system infection by SARS­CoV­2: Entry mechanism, clinical symptoms and expression of major receptors (Review).

Besides causing severe acute respiratory syndrome (SARS), SARS­coronavirus 2 (SARS­CoV­2) also harms the digestive system. Given the appearance of numerous cases of SARS­CoV­2, it has been demonstrated that SARS­CoV­2 is able to harm target organs such as the gastrointestinal tract, liver and pancreas, and either worsen the condition of patients with basic digestive illnesses or make their prognosis poor. According to several previously published studies, angiotensin­converting enzyme II (ACE2) and transmembrane serine protease II (TMPRSS2) are expressed either singly or in combination in the digestive system and in other regions of the human body. In order to change the viral conformation, create a fusion hole and release viral RNA into the host cell for replication and transcription, SARS­CoV­2 is capable of binding to these two proteins through the spike protein on its surface. As a result, the body experiences an immune reaction and an inflammatory reaction, which may lead to nausea, diarrhea, abdominal pain and even gastrointestinal bleeding, elevated levels of liver enzymes, acute liver injury, pancreatitis and other serious lesions. In order to provide possible strategies for the clinical diagnosis and treatment of digestive system diseases during the COVID­19 pandemic, the molecular structure of SARS­CoV­2 and the mechanism via which SARS­CoV­2 enters the human body through ACE2 and TMPRSS2 were discussed in the present review, and the clinical manifestations of SARS­CoV­2 infection in the digestive system were also summarized. Finally, the expression characteristics of ACE2 and TMPRSS2 in the main target organs of the digestive system were described.

FUT6 inhibits the proliferation, migration, invasion, and EGF-induced EMT of head and neck squamous cell carcinoma (HNSCC) by regulating EGFR/ERK/STAT signaling pathway.

Glycosylation change is one of the landmark events of tumor occurrence and development, and tumor cells may be inhibited by regulating the aberrant expression of glycosyltransferases. Currently, fucosyltransferase VI (FUT6), which is involved in the synthesis of α-1, 3 fucosyl bond, has been detected to be closely associated with multiple tumors, but its function and mechanism in head and neck squamous cell carcinoma (HNSCC) still need further research. In this study, FUT6 knockdown and overexpression strategies were used to investigate the effects of FUT6 on cell proliferation, migration, and invasion, as well as the growth and metastasis of HNSCC in a xenografts mouse model. The protein expression levels of epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK), Signal Transducer and Activator of Transcription (STAT), protein kinase B (AKT), c-Myc, and epithelial-mesenchymal transition (EMT) markers were determined by western blot analysis. Our research found that the mRNA expression of FUT6 was lower in HNSCC tissues than in normal mucosal epithelial tissues. In Cal-27 and FaDu cells, FUT6 overexpression inhibited cell proliferation, migration and invasion, causing upregulation of ZO-1 and E-cadherin, downregulation of N-cadherin and Vimentin, and finally decreased the phosphorylation levels of EGFR, ERK, STAT, and c-Myc. In HSC-3 cells, knockdown of FUT6 promoted cell proliferation, migration and invasion, downregulating ZO-1 and E-cadherin, upregulating N-cadherin and Vimentin, and increased the phosphorylation levels of EGFR, ERK, STAT, and c-Myc. In the HNSCC xenografts mouse, FUT6 overexpression inhibited tumor growth and metastasis. In summary, FUT6 controls the proliferation, migration, invasion, and EGF-induced EMT of HNSCC by regulating EGFR/ERK/STAT signaling pathway, indicating its potential future therapeutic application for HNSCC.

FAM3 Family as Prognostic Factors for Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Although head and neck squamous cell carcinoma (HNSCC) is a common malignancy, the molecular biology landscape underlying its occurrence and development remains poorly understood. The family with sequence similarity (FAM) 3 family of proteins includes four family members, namely FAM3A, FAM3B, FAM3C and FAM3D. In particular, FAM3C has been previously reported to be closely associated with various human malignancies. METHODS: Combining analyses using The Cancer Genome Atlas, Gene Expression Profiling Interactive Analysis, Tumor Immune Estimation Resource and MethSurv databases, coupled with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes bioinformatics tools, the possible biological function and key pathways regulated by the FAM3 family in HNSCC were probed. RESULTS: High FAM3A expression was found to increase HNSCC mitochondrial biosynthesis and energy metabolism, inhibit immune cell infiltration in the HNSCC tumor microenvironment, and be associated with poor prognosis. By contrast, lower expression levels of FAM3B in HNSCC were associated with a poorer prognosis in patients with HNSCC. This was most likely due to the finding that FAM3B can inhibit the development of HNSCC by increasing immune cell infiltration, inhibiting epithelial-mesenchymal transition (EMT) and the cytochrome P450 pathway. FAM3C was overexpressed in oral squamous cell carcinoma (OSCC) and associated with increased OSCC cell stemness, immune escape and EMT. In the present study, FAM3C expression was associated with poor prognosis for patients with HNSCC by suppressing tumor immune cell infiltration. FAM3C expression was also positively correlated with the expression of epithelial and mesenchymal markers such as E-cadherin, N-cadherin, Vimentin and ZO-1, which may promote the partial EMT status in HNSCC and greatly increase its malignancy. FAM3D is a maintenance factor of the epithelial phenotype in HNSCC that can inhibit the progression of EMT, promote tumor immune cell infiltration and inhibit HNSCC progression. In addition, methylation levels of the FAM3 gene family were correlated with the overall survival rate of HNSCC. CONCLUSION: The FAM3 family may be applied as a biomarker and potential therapeutic target for HNSCC.

Renewed understanding of nicotinic acid and its derivatives: from traditional nutrients to cancer prevention and treatment / 中国肿瘤生物治疗杂志

@#[摘 要] 烟酸属于B族维生素，是人体必需的维生素之一。过去对烟酸功能的认知主要停留在营养素层面，如参与维持神经功能、促进代谢和发育、保护心脑血管等。随着研究的不断深入，近年来已有多项研究表明，烟酸及其衍生物能起到预防和辅助治疗癌症的作用。烟酸及其衍生物不仅影响肿瘤细胞的生物学功能、参与免疫调节，还能对烟酰胺磷酸核糖转移酶（NAMPT）抑制剂的抗肿瘤疗效起到辅助作用，并以多聚ADP-核糖聚合酶（PARP）依赖方式通过多种分子途径维持基因组的稳定性。本文总结了烟酸及其衍生物在肿瘤中作用的研究脉络和最新进展，并展望其进一步研究和应用方向，对烟酸及其衍生物在肿瘤综合防治中的应用有一定的指导作用。

APOBEC3B: Future direction of liver cancer research.

Liver cancer is one of the most common cancers in the world, and the rate of liver cancer is high due to the of its illness. The main risk factor for liver cancer is infection with the hepatitis B virus (HBV), but a considerable number of genetic and epigenetic factors are also directly or indirectly involved in the underlying pathogenesis of liver cancer. In particular, the apolipoprotein B mRNA editing enzyme, catalytic peptide-like protein (APOBEC) family (DNA or mRNA editor family), which has been the focus of virology research for more than a decade, has been found to play a significant role in the occurrence and development of various cancers, providing a new direction for the research of liver cancer. APOBEC3B is a cytosine deaminase that controls a variety of biological processes, such as protein expression, innate immunity, and embryonic development, by participating in the process of cytidine deamination to uridine in DNA and RNA. In humans, APOBEC3B has long been known as a DNA editor for limiting viral replication and transcription. APOBEC3B is widely expressed at low levels in a variety of normal tissues and organs, but it is significantly upregulated in different types of tumor tissues and tumor lines. Thus, APOBEC3B has received increasing attention in various cancers, but the role of APOBEC3B in the occurrence and development of liver cancer due to infection with HBV remains unclear. This review provides a brief introduction to the pathogenesis of hepatocellular carcinoma induced by HBV, and it further explores the latest results of APOBEC3B research in the development of HBV and liver cancer, thereby providing new directions and strategies for the treatment and prevention of liver cancer.

Physiological and pathological roles of Hic­5 in several organs (Review).

Integrins allow cells to adhere to the extracellular matrix and promote the recruitment of other integrins, resulting in the formation of focal adhesion sites at the binding sites. Focal adhesion sites play essential roles in the assembly of the cytoskeleton and are vital in shaping the structure of cells. They also play other regulatory roles by influencing numerous biological functions, such as cell proliferation and apoptosis. Hydrogen peroxide­inducible clone 5 (Hic­5) is a member of the Paxillin family of proteins and is an adhesive plaque scaffolding protein. Its expression can be detected in both vascular and smooth muscle cells. Thus, it plays an essential role in vascular remodeling, as well as in fibrotic diseases. Hic­5 functions as a coactivator of steroid receptors, thus playing a role in steroid hormone­dependent diseases. It also plays a vital role in the invasive metastasis of various types of cancer. Moreover, several studies have demonstrated that Hic­5 plays a critical role in transcriptional regulation, as well as in numerous signaling pathways. Therefore, the inhibition of the functions of Hic­5 may prevent the development or halt the progression of several diseases. Its use as a therapeutic target in future investigations may thus aid in the treatment of several diseases, including various types of cancer. The present review article focused on the expression and functions of Hic­5 in different organs, with the aim of highlighting novel possibilities for future research.

CD44 Glycosylation as a Therapeutic Target in Oncology.

The interaction of non-kinase transmembrane glycoprotein CD44 with ligands including hyaluronic acid (HA) is closely related to the occurrence and development of tumors. Changes in CD44 glycosylation can regulate its binding to HA, Siglec-15, fibronectin, TM4SF5, PRG4, FGF2, collagen and podoplanin and activate or inhibit c-Src/STAT3/Twist1/Bmi1, PI3K/AKT/mTOR, ERK/NF-κB/NANOG and other signaling pathways, thereby having a profound impact on the tumor microenvironment and tumor cell fate. However, the glycosylation of CD44 is complex and largely unknown, and the current understanding of how CD44 glycosylation affects tumors is limited. These issues must be addressed before targeted CD44 glycosylation can be applied to treat human cancers.

Pathology and physiology of acid­sensitive ion channels in the digestive system (Review).

As a major proton­gated cation channel, acid­sensitive ion channels (ASICs) can perceive large extracellular pH changes. ASICs play an important role in the occurrence and development of diseases of various organs and tissues including in the heart, brain, and gastrointestinal tract, as well as in tumor proliferation, invasion, and metastasis in acidosis and regulation of an acidic microenvironment. The permeability of ASICs to sodium and calcium ions is the basis of their physiological and pathological roles in the body. This review summarizes the physiological and pathological mechanisms of ASICs in digestive system diseases, which plays an important role in the early diagnosis, treatment, and prognosis of digestive system diseases related to ASIC expression.

SLC26A9 deficiency causes gastric intraepithelial neoplasia in mice and aggressive gastric cancer in humans.

BACKGROUND: Solute carrier family 26 member (SLC26A9) is a Cl- uniporter with very high expression levels in the gastric mucosa. Here, we describe morphological and molecular alterations in gastric mucosa of slc26a9-/- mice and in selective parietal cell-deleted slc26a9fl/fl/Atp4b-Cre mice and correlate SLC26A9 expression levels with morphological and clinical parameters in a cohort of gastric cancer (GC) patients. METHODS: The expression patterns of genes related to transport and enzymatic function, proliferation, apoptosis, inflammation, barrier integrity, metaplasia and neoplasia development were studied by immunohistochemistry (IHC), quantitative RT-PCR, in situ hybridization and RNA microarray analysis. SLC26A9 expression and cellular/clinical phenotypes were studied in primary human GC tissues and GC cell lines. RESULTS: We found that both complete and parietal cell-selective Slc26a9 deletion in mice caused spontaneous development of gastric premalignant and malignant lesions. Dysregulated differentiation of gastric stem cells in an inflammatory environment, activated Wnt signaling, cellular hyperproliferation, apoptosis inhibition and metaplasia were observed. Analysis of human gastric precancerous and cancerous tissues revealed that SLC26A9 expression progressively decreased from atrophic gastritis to GC, and that downregulation of SLC26A9 was correlated with patient survival. Exogenous expression of SLC26A9 in GC cells induced upregulation of the Cl-/HCO3- exchanger AE2, G2/M cell cycle arrest and apoptosis and suppressed their proliferation, migration and invasion. CONCLUSIONS: Our data indicate that SLC26A9 deletion in parietal cells is sufficient to trigger gastric metaplasia and the development of neoplastic lesions. In addition, we found that SLC26A9 expression decreases during human gastric carcinogenesis, and that exogenous SLC26A9 expression in GC cells reduces their malignant behavior.

The source of the fat significantly affects the results of high-fat diet intervention.

High-fat diet (HFD) is widely used in animal models of many diseases, it helps to understand the pathogenic mechanism of related diseases. Several dietary fats were commonly used in HFD, such as corn oil, peanut oil, soybean oil, sunflower oil, and lard. However, it was reported that different dietary fat could have completely different effects on physiological indicators and the gut microbiome, and the sources of dietary fat used in high-fat diet research have not been comprehensively compared. In this research, we conduct comparative experiments on various sources of dietary fats to test their different effects during the high-fat diet intervention. We investigated the effects of twelve common dietary fats in high-fat diet intervention of mice, body/liver weight changes, four blood lipid indices, and gut microbiome were analyzed. Our results showed that the source of dietary fat used in high-fat diet significantly affects the changes of body/liver weight and triglyceride (TRIG) in the blood. Furthermore, the intervention of canola oil increased the alpha diversity of gut microbiota, and lard has decreased diversity compared with the control group. The composition of saturated fatty acid (SFA) in fat has the most significant effects on the gut microbiome. All dietary fats treatments have an increasing Firmicutes abundance and a reduced Bacteroidetes abundance in gut microbiome, while the canola oil has a slight variation compared to other intervention groups, and the lard group has the largest changes. This study showed that different types of dietary fat have different effects on the body indicators and intestinal microbiota of mice, and canola oil produced less disturbance than other types of dietary fats in high-fat diet.

SPINKs in Tumors: Potential Therapeutic Targets.

The serine protease inhibitor Kazal type (SPINK) family includes SPINK1-14 and is the largest branch in the serine protease inhibitor family. SPINKs play an important role in pancreatic physiology and disease, sperm maturation and capacitation, Nager syndrome, inflammation and the skin barrier. Evidence shows that the unregulated expression of SPINK1, 2, 4, 5, 6, 7, and 13 is closely related to human tumors. Different SPINKs exhibit various regulatory modes in different tumors and can be used as tumor prognostic markers. This article reviews the role of SPINK1, 2, 4, 5, 6, 7, and 13 in different human cancer processes and helps to identify new cancer treatment targets.

The risk of nonsyndromic cleft lip with or without cleft palate and Vax1 rs7078160 polymorphisms in southern Han Chinese / Risco de fenda labial não sindrômica com ou sem fenda palatina e polimorfismo Vax1 rs7078160 em indivíduos da etnia Han do sul da China

Abstract Introduction: Non-syndromic cleft lip with or without cleft palate is a common worldwide birth defect due to a combination of environmental and genetic factors. Genome-wide association studies reported the rs7078160 of Vax1 is closely related to non-syndromic cleft lip with or without cleft palate in European populations. The following studies showed the same results in Mongolian, Japanese, Filipino, Vietnamese populations etc. However, conflicting research had been reported in Chinese population, Objective: The aim of this study was to investigate the association between the rs7078160 polymorphism and non-syndromic cleft lip with or without cleft palate in Southern Chinese patients. Methods: In this study, we investigated the polymorphism distribution of rs7078160 in 100 complete patient trios (39 patients with non-syndromic cleft lip and palate; 36 patients with non-syndromic cleft lip only; 25 had non-syndromic cleft palate only; and their parents) from Southern ethnic Han Chinese. 60 healthy trios were selected as control. Polymerase chain reaction and Sanger sequencing were used to genotype rs7078160 in Vax1; both case-control and family-based associations were analyzed. Results: The case-control analyses revealed the rs7078160 polymorphism was significant, associated with non-syndromic cleft lip with or without cleft palate (p = 0.04) and non-syndromic cleft lip and palate (p = 0.01), but not associated with non-syndromic cleft lip only and nonsyndromic cleft palate only patients. The genotype composition of rs7078160 comprises mutated homozygous AA, heterozygous AG and wild homozygous GG. Cases with AG + AA genotypes compared with GG homozygotes showed an increased risk of non-syndromic cleft lip with or without cleft palate (p = 0.04, OR = 2.05, 95% CI: 1.01-4.16) and non-syndromic cleft lip and palate (p = 0.01, OR = 3.94, 95% CI: 1.34-11.54). In addition, we did not detect any transmissiondisequilibrium in rs7078160 (p = 0.68). Conclusion: This study suggests that rs7078160 polymorphism is a risk factor of non-syndromic cleft lip with or without cleft palate, and Vax1 is strongly associated with non-syndromic cleft lip with or without cleft palate in Southern Chinese Han populations.

Resumo Introdução: A fenda labial não sindrômica, com ou sem fenda palatina, é um defeito congênito comum em todo o mundo, devido a uma combinação de fatores ambientais e genéticos. O genome-wide association studies relatou que o polimorfismo rs7078160 do Vax1 está intimamente relacionado à fenda labial não sindrômica, com ou sem fenda palatina em populações europeias. Estudos subsequentes mostraram os mesmos resultados nas populações mongol, japonesa, filipina e vietnamita etc. No entanto, pesquisas conflitantes foram relatadas na população chinesa. Objetivo: Investigar a associação entre o polimorfismo rs7078160 e fenda labial não sindrômica, com ou sem fenda palatina, em pacientes do sul da China. Método: Tentamos investigar a distribuição do polimorfismo rs7078160 em 100 trios completos de pacientes (39 pacientes com fenda labial e palatina não sindrômica; 36 pacientes com fenda labial somente, não sindrômica; 25 com fenda palatina somente, não sindrômica e seus pais), da etnia Han do sul da China, e em 60 trios saudáveis selecionados como controle. Reação de polimerase em cadeia e o sequenciamento de Sanger foram uszados para genotipar o polimorfismo rs7078160 do Vax1 e tanto os casos-controle quanto as associações baseadas na família foram analisadas. Resultados: As análises de caso-controle revelaram que o polimorfismo rs7078160 estava significativamente associado a fenda labial não sindrômica, com ou sem fenda palatina (p = 0,04) e fenda labial e palatina não sindrômica (p = 0,01), mas não estava associado a pacientes com fenda labial somente não sindrômica e fenda palatina somente não sindrômica. A composição do genótipo de rs7078160 compreende AA homozigoto mutado, AG heterozigoto e GG homozigoto selvagem. Casos com genótipos AG + AA comparados com GG homozigotos mostraram um risco aumentado de fenda labial não sindrômica, com ou sem fenda palatina (p = 0,04, OR = 2,05, IC de 95%: 1,01 ± 4,16) e fenda labial e palatina não sindrômica (p = 0,01, OR = 3,94, IC 95%: 1,34-11,54). Além disso, não detectamos desequilíbrio de transmissão em rs7078160 (p = 0,68). Conclusão: Este estudo sugere que o polimorfismo rs7078160 foi um fator de risco para fenda labial não sindrômica, com ou sem fenda palatina, e o gene Vax1 está fortemente associado com fenda labial não sindrômica, com ou sem fenda palatina em populações da etnia Han do sul da China.

The role of corticotropin-releasing hormone (CRH) family in tumors.

The corticotropin-releasing hormone (CRH) family is widely distributed among the central nervous system and peripheral tissues, such as the digestive, cardiovascular, immune, reproductive, endocrine systems. The CRH family members are widely involved in the regulation of human cell biological processes, immune response, and regulation of inflammatory processes that can affect the occurrence and development of tumors. At present, CRH family members and their receptors can be detected in many tumor tissues, and some people think that members of the CRH family may be potential tumor treatment targets as they can affect cellular processes, such as proliferation, migration, invasion, and apoptosis. However currently, there is no systematic introduction to the relationship between the CRH family and various tumors. This review introduces the molecular regulation of the CRH family in tumor formation and seeks further targeted therapy.

SLC26A6 and NADC­1: Future direction of nephrolithiasis and calculus­related hypertension research (Review).

Nephrolithiasis is the most common type of urinary system disease in developed countries, with high morbidity and recurrence rates. Nephrolithiasis is a serious health problem, which eventually leads to the loss of renal function and is closely related to hypertension. Modern medicine has adopted minimally invasive surgery for the management of kidney stones, but this does not resolve the root of the problem. Thus, nephrolithiasis remains a major public health issue, the causes of which remain largely unknown. Researchers have attempted to determine the causes and therapeutic targets of kidney stones and calculus­related hypertension. Solute carrier family 26 member 6 (SLC26A6), a member of the well­conserved solute carrier family 26, is highly expressed in the kidney and intestines, and it primarily mediates the transport of various anions, including OXa2­, HCO3­, Cl­ and SO42­, amongst others. Na+­dependent dicarboxylate­1 (NADC­1) is the Na+­carboxylate co­transporter of the SLC13 gene family, which primarily mediates the co­transport of Na+ and tricarboxylic acid cycle intermediates, such as citrate and succinate, amongst others. Studies have shown that Ca2+ oxalate kidney stones are the most prevalent type of kidney stones. Hyperoxaluria and hypocitraturia notably increase the risk of forming Ca2+ oxalate kidney stones, and the increase in succinate in the juxtaglomerular device can stimulate renin secretion and lead to hypertension. Whilst it is known that it is important to maintain the dynamic equilibrium of oxalate and citrate in the kidney, the synergistic molecular mechanisms underlying the transport of oxalate and citrate across kidney epithelial cells have undergone limited investigations. The present review examines the results from early reports studying oxalate transport and citrate transport in the kidney, describing the synergistic molecular mechanisms of SLC26A6 and NADC­1 in the process of nephrolithiasis formation. A growing body of research has shown that nephrolithiasis is intricately associated with hypertension. Additionally, the recent investigations into the mediation of succinate via regulation of the synergistic molecular mechanism between the SLC26A6 and NADC­1 transporters is summarized, revealing their functional role and their close association with the inositol triphosphate receptor­binding protein to regulate blood pressure.

Partial EMT in Squamous Cell Carcinoma: A Snapshot.

In the process of cancer EMT, some subgroups of cancer cells simultaneously exhibit both mesenchymal and epithelial characteristics, a phenomenon termed partial EMT (pEMT). pEMT is a plastic state in which cells coexpress epithelial and mesenchymal markers. In squamous cell carcinoma (SCC), pEMT is regulated, and the phenotype is maintained via the HIPPO pathway, NOTCH pathway and TGF-ß pathways and by microRNAs, lncRNAs and the cancer microenvironment (CME); thus, SCC exhibits aggressive tumorigenic properties and high stemness, which leads collective migration and therapy resistance. Few studies have reported therapeutic interventions to address cells that have undergone pEMT, and this approach may be an effective way to inhibit the plasticity, drug resistance and metastatic potential of SCC.

Role of the S100 protein family in liver disease (Review).

Liver disease is a significant health challenge worldwide and comprises liver fibrosis and cirrhosis, viral hepatitis, fatty liver, non­alcoholic fatty liver disease, alcoholic liver disease and hepatocellular carcinoma (HCC). Due to the lack of effective treatments, the prognosis of end­stage liver disease (including advanced liver cirrhosis and HCC) is often poor. S100 proteins are a type of Ca2+ binding protein, which are expressed in a cell­specific manner in vertebrates. These proteins are involved in numerous functions, such as serving as intracellular Ca2+ sensors, transduction of Ca2+ signals and regulation of extracellular factors that affect cellular activity by binding to a range of membrane receptors. Evidence has shown that S100 proteins serve key roles in the occurrence and development of liver disease and can be used as potential therapeutic targets or diagnosis markers. For example, certain studies have suggested that blocking S100 protein expression may be an innovative treatment strategy. The present review focuses on the functions of the S100 protein family in liver disease.