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[Display omitted] • HIGD1A and ZG16, lower expressed in COAD than in READ, are both associated with poor prognosis in COAD, but not in READ. • Compared with ZG16, HIGD1A showed more efficiency in suppressing tumor growth and metastasis in CRC cells. • miR-501-3p, higher expressed in COAD than in READ, promoted CRC cells proliferation, invasion, and migration through suppressing HIGD1A expression. • High leveled miR-501-3p inhibited HIGD1A expression in COAD, which promoted tumor growth and metastasis, and eventually caused poor prognosis in COAD. • Procyanidin C1 (PCC1), a kind of natural polyphenol has been verified as a potential miR-501-3p inhibitor, which modulated miR-501-3p/HIGD1A axis and inhibited tumor growth and metastasis in vivo and in vitro. Although colon (COAD) and rectal adenocarcinoma (READ) combined to refer to colorectal cancer (CRC), substantial clinical evidence urged that CRC should be treated as two different cancers due to compared with READ, COAD showed higher morbidity and worse 5-year survival. This study has tried to screen for the crucial gene that caused the worse prognosis and investigate its mechanism for mediating tumor growth and metastases in COAD. Meanwhile, the potential anti-COAD compound implicated in this mechanism was identified and testified from 1,855 food-borne chemical kits. This study aims to bring a new perspective to the development of new anti-COAD drugs and personalized medicine for patients with COAD. The survival-related hub genes in COAD and READ were screened out from The Cancer Genome Atlas (TCGA) database and the results showed that HIGD1A , lower expressed in COAD than in READ, was associated with poor prognosis in COAD patients, but not in READ. Over-expressed HIGD1A suppressed CRC cell proliferation, invasion, and migration in vitro and in vivo. Meanwhile, the different expressed microRNA profiles between COAD and READ showed that miR-501-3p was highly expressed in COAD and inhibited HIGD1A expression by targeting 3′UTR of HIGD1A. MiR-501-3p mimics promoted cell proliferation and metastasis in CRC cells. In addition, Procyanidin C1 (PCC1), a kind of natural polyphenol has been verified as a potential miR-501-3p inhibitor. In vitro and in vivo , PCC1 promoted HIGD1A expression by suppressing miR-501-3p and resulted in inhibited tumor growth and metastasis. The present study verified that miR-501-3p/HIGD1A axis mediated tumor growth and metastasis in COAD. PCC1, a flavonoid that riched in food exerts anti-COAD effects by inhibiting miR-501-3p and results in the latter losing the ability to suppress HIGD1A expression. Subsequently, unfettered HIGD1A inhibited tumor growth and metastasis in COAD. [ABSTRACT FROM AUTHOR]

Shen-Qi-Jiang-Tang granule (SQJTG), a classic traditional Chinese medicine (TCM) prescription, has been widely used in clinical for diabetes, especially type Ⅱ diabetes. Previous anti-diabetic studies stumbled across that SQJTG has a potential kidney protective effect on diabetic nephropathy (DN). However, the protective mechanism of SQJTG on DN still needs to be explored. The purpose of the present study was to explore the therapeutic effect of SQJTG on DN through both bioinformatics analysis and in vivo experiments. The TCMIP database was used for screening potential compounds and targets of SQJTG, and the GeneCards, OMIM, DrugBank, and TTD databases were used for collecting DN-related genes. Then protein-protein interaction analysis for the common targets of SQJTG and DN was performed by the STRING database. Meanwhile, KEGG and GO were carried out using the Metascape and DAVID databases. In vivo experiments, to testify the potential kidney protective effects of SQJTG, STZ-induced DN mice with different dosages of SQJTG treatment were collected and the renal tissues were detected by H&E, PAS, Masson and TUNEL staining. Immunohistochemistry and immunoblotting were used to assess the proteins' expressions. Flow cytometry and ELISA assay were used to detect the levels of pro-inflammatory cytokines. Among the 338 compounds ascertained by SQJTG, there were 789 related targets as well. Moreover, 1,221 DN-related targets were predicted and 20 core targets were screened by the PPI analyses. According to GO and KEGG pathway analysis, SQJTG may affect DN via the TNF pathway. For the in vivo experiments, renal histomorphological examinations demonstrated that SQJTG treatment significantly ameliorated STZ-induced kidney damage and had a dosage dependence. Meanwhile, mice with DN were found to have dramatic increases in IL-1, TNF-α, IL-6, and IL-12, but markedly decreased after administration of SQJTG. In addition, the protein levels of TNF signaling molecules, like p-P65, p-JNK, and p-p38, showed significantly elevated in kidney tissues of DN mice and attenuated after SQJTG treatment. SQJTG exerts a kidney protective effect in DN mice via modulating TNF signaling pathways, and it has promising applications for the treatment of DN. [Display omitted] • 338 compounds ascertained from SQJTG targeted 789 genes and 133 genes were diabetic nephropathy (DN)-related. • GO and KEGG pathway analysis predicted that SQJTG may affect DN via TNF pathway. • In vivo , SQJTG significantly ameliorated STZ-induced kidney damage via inhibited IL-1, TNF-α, IL-6, and IL-12 levels. • SQJTG relieved STZ-activated TNF signaling pathway by down-regulated p-P65, p-JNK, and p-p38 expressions in STZ-mice. [ABSTRACT FROM AUTHOR]