Performance and characterization of 94 identity-informative SNPs in Northern Han Chinese using ForenSeq ™ DNA signature prep kit.

Target and flanking region (FR) variation at 94 identity-informative SNPs (iSNPs) are investigated in 635 Northern Han Chinese using the ForenSeq DNA Signature Prep Kit on the MiSeq FGx Forensic Genomics System. The dataset presents the following performance characteristics (average values): ≥60% bases with a quality score of 20 or higher (%≥ Q20); >700 × of depth of coverage (DoC) from both Sample Details Reports and Flanking Region Reports; >80% of effective reads; ≥60% of allele coverage ratio (ACR); and ≥70% of inter-locus balance, while some stable low-performance characteristics are also observed: low DoC at rs1736442, rs1031825, rs7041158, rs338882, rs2920816, rs1493232, rs719366, and rs2342747; high noise at rs891700; and imbalanced ACR at rs6955448 and rs338882. The average amplicon length is 69 bp, suitable for detecting degraded samples. Bioinformatic concordance achieves 99.99% between the ForenSeq Universal Analysis Software (UAS) and the Integrative Genomic Viewer (IGV) inspection. Discordance results from flanking region deletions of rs10776839, rs8078417, rs2831700, and rs1454361. Due to FR variants within amplicons detected by massively parallel sequencing (MPS), the increases in the number of unique alleles, effective alleles (Ae), and observed heterozygosity (Hobs) are 46.81%, 4.51%, and 3.29%, respectively. Twelve FR variants are first reported to dbSNP, such as rs1252699848, rs1665500714, rs1771121532, rs2097285015, rs1851671415, rs2045669877, rs2046758811, rs2044248635, rs1251308240, rs1968822112, rs1981638299, and rs1341756746. All 94 iSNPs from target and amplicon data are in Hardy-Weinberg equilibrium (HWE) and independent within autosomes. As expected, forensic parameters from the amplicon data increase significantly on the combined power of discrimination (CPD = 1 - 3.9876 × 10-38) and the combined power of exclusion (CPE = 1 - 6.6690 × 10-8). Additionally, the power of the system effectiveness (CPD = 1 - 6.7054 × 10-72 and CPE = 1 - 4.4719 × 10-20) with sequence-based 27 autosomal STRs and 94 iSNP amplicons in combination is substantially improved compared to one type of marker alone. In conclusion, we have established a traditional length-based and current sequence-based reference database with 58 STRs and 94 iSNPs in the Northern Han Chinese population. We hope these data can serve as a solid reference and foundation for forensic practice.

Sequence-based mutation patterns at 41 Y chromosomal STRs in 2 548 father-son pairs.

A total of 2 548 unrelated healthy father-son pairs from a Northern Han Chinese population were genotyped at 41 Y chromosomal short tandem repeat (Y-STRs) including DYS19, DYS388, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS444, DYS447, DYS448, DYS449, DYS456, DYS458, DYS460, DYS481, DYS518, DYS522, DYS549, DYS533, DYS557, DYS570, DYS576, DYS593, DYS596, DYS627, DYS635, DYS643, DYS645, Y-GATA-H4, DYF387S1a/b, DYF404S1a/b, DYS385a/b, and DYS527a/b. In 2 548 father samples, 2 387 unique haplotypes were detected with the haplotype diversity and discrimination capacity values of 0.999 956 608 and 0.96 741 007. The average gene diversity (GD) value was 0.6934 with a range from 0.1051 at DYS645 to 0.9657 at DYS385a/b. When comparing alleles at 24 overlapped Y-STRs between the ForenSeq™ deoxyribonucleic acid (DNA) Signature Prep Kit on the MiSeq FGx® Forensic Genomics System and the Goldeneye® DNA ID Y Plus Kit on the Applied Biosystems™ 3730 DNA Analyzer from 308 father samples in mutational pairs, 258 alleles were detected by massively parallel sequencing (MPS) typing including 156 length-based alleles that could be obtained by capillary electrophoresis (CE) typing, 95 repeat region (RR) variant alleles and seven flanking region variant alleles. Hereof, we found 16 novel RR variant alleles and firstly identified two SNPs (rs2016239814 at DYS19 and rs2089968964 at DYS448) and one 4-bp deletion (rs2053269960 at DYS439) that had been validated by the Database of Short Genetic Variation. Sanger sequencing or MPS was employed to confirm 356 mutations from 104 468 allele transfers generated from CE, where 96.63% resulted in one-step mutations, 2.25% in two-step, and 1.12% in multi-step, and the overall ratio of repeat gains versus losses was balanced (173 gains vs. 183 losses). In 308 father-son pairs, 268 pairs occurred mutations at a single locus, 33 pairs at two loci, six pairs at three loci, and one pair at four loci. The average Y-STR mutation rate at 41 Y-STRs was ⁓3.4 × 10-3 (95% confidence intervals: 3.1 × 10-3-3.8 × 10-3). The mutation rates at DYS576 and DYS627 were higher than 1 × 10-2 in Northern Han Chinese, whilst the mutation rates at DYF387S1a/b, DYF404S1a/b, DYS449, DYS518, and DYS570 were lower than initially defined. In this study, the classical molecular factors (the longer STR region, the more complex motif and the order father) were confirmed to drive Y-STR mutation rates increased, but the length of repeat unit did not conform to the convention. Lastly, the interactive graphical and installable StatsY was developed to facilitate forensic scientists to automatically calculate allele and haplotype frequencies, forensic parameters, and mutation rates at Y-STRs. Key points: 308 of 2 548 father-son pairs from Northern Han Chinese occurred at least one mutation(s) across 41 Y-STRs.Sanger sequencing or MPS was employed to confirm those mutations generated from CE.The longer STR region, the more complex motif and the order father drove Y-STR mutation rates increased.StatsY was developed to calculate allele and haplotype frequencies, forensic parameters and mutation rates at Y-STRs.

SLC3A2, as an indirect target gene of ALDH2, exacerbates alcohol-associated liver cancer via the sphingolipid biosynthesis pathway.

Excessive drinking is one of the main causes of liver cancer. In the process of alcohol metabolism, aldehyde dehydrogenase 2 (ALDH2) is the key enzyme of acetaldehyde metabolism. ALDH2 gene deficiency is positively associated with the risk of hepatocellular carcinoma (HCC). However, no studies have shown a connection between ALDH2 and another metabolic regulatory gene, SLC3A2. In this study, we analyzed the expression levels of ALDH2 and SLC3A2 in liver cancer tissues based on the TCGA database. Subsequently, we constructed ALDH2 knockout and SLC3A2 knock-in transgenic mice to check the roles of ALDH2 and SLC3A2 in tumorigenesis in vivo. In addition, we examined the mechanisms of ALDH2 and SLC3A2 in HCC cells using small RNA interference technology. Consistent with previous studies, we also confirmed the functions of ALDH2 in inhibiting hepatocarcinogenesis, while SLC3A2 had the opposite effect. The main finding of this study is that ALDH2 inhibited BSG expression through the TGF-ß1 pathway, which indirectly inhibited SLC3A2 expression; subsequently, the sphingolipid metabolism pathway was also inhibited in HCC cells. Therefore, SLC3A2 is a novel target for HCC treatment.

High-resolution genotyping of 58 STRs in 635 Northern Han Chinese with MiSeq FGx ® Forensic Genomics System.

Sequence polymorphisms were characterized at 27 autosomal STRs (A-STRs), 7 X chromosomal STRs (X-STRs), and 24 Y chromosomal STRs (Y-STRs) in 635 Northern Han Chinese with the ForenSeq DNA Signature Prep Kit on the MiSeq FGx Forensic Genomics System. Since repeat region (RR) and flanking region (FR) variation can be detected by massively parallel sequencing (MPS), the increase in the number of unique alleles and the average of gene diversity was 78.18% and 3.51% between sequence and length, respectively. A total of 74 novel RR variants were identified at 33 STRs compared with STRSeq and previous studies, and 13 FR variants (rs1770275883, rs2053373277, rs2082557941, rs1925525766, rs1926380862, rs1569322793, rs2051848492, rs2051848696, rs2016239814, rs2053269960, rs2044518192, rs2044536444, and rs2089968964) were first submitted to dbSNP. Also, 99.94% of alleles were concordant between the ForenSeq DNA Signature Prep Kit and commercial CE kits. Discordance resulted from the low performance at D22S1045 and occasionally at DYS392, flanking region deletions at D7S820 and DXS10074, and the strict alignment algorithm at DXS7132. Null alleles at DYS505 and DYS448 and multialleles at DYS387S1a/b, DYS385a/b, DYS448, DYS505, DXS7132, and HPRTB were validated with other MPS and CE kits. Thus, a high-resolution sequence-based (SB) and length-based (LB) allele frequencies dataset from Northern Han Chinese has been established already. As expected, forensic parameters increased significantly on combined power of discrimination (PD) and combined power of exclusion (PE) at A-STRs, mildly on combined PD and combined mean exclusion chance (MEC) at X-STRs, and barely on discrimination capacity (DC) at Y-STRs. Additionally, MiSeq FGx quality metrics and MPS performance were evaluated in this study, which presented the high-quality of the dataset at 20 consecutive runs, such as ≥ 60% bases with a quality score of 20 or higher (%≥ Q20), > 60% of effective reads, > 2000 × of depth of coverage (DoC), ≥ 60% of allele coverage ratio (ACR) or heterozygote balance, ≥ 70% of inter-locus balance, and ≤ 0.4 of the absolute value of observed minus expected heterozygosity (|Hexp - Hobs|). In conclusion, MiSeq FGx can help us generate a high-resolution and high-quality dataset for human identification and population genetic studies.

Human leukocyte antigen and tumor immunotherapy (Review).

Malignant tumors seriously endanger human health and life, and restrict economic development. Human leukocyte antigen (HLA) is the expression product of the human major histocompatibility complex, which, at present, is the most complex known polymorphic system. The polymorphism and expression of HLA molecules have been demonstrated to be associated with the occurrence and development of tumors. HLA molecules can regulate the proliferation of tumor cells and inhibit antitumor immunity. In the present review, the structure and function of HLA molecules, the polymorphism and expression of HLA in tumor tissue, the roles of HLA in tumor cells and tumor immunity, and the potential clinical application of HLA in tumor immunotherapy are summarized. The overall aim of the present review is to provide relevant information for the development of antitumor immunotherapies involving HLA in the clinic.

Different races have different immune microenvironments: comparison of White and Asian patients with liver cancer.

Different ethnic groups have different incidence rate of hepatocellular carcinoma (HCC). In addition to lifestyle and environmental factors, genetic susceptibility is also an important reason. In this study, we screened the immune related genes and stromal related genes in White and Asian liver cancer patients cohort of The Cancer Genome Atlas (TCGA) the using ESTIMATE algorithm. Hub genes that significantly associated with overall survival (OS) were selected from White and Asian liver cancer patients, respectively. In addition, we validated the functions of two hub genes, IL-18RAP and GPM6A, in vivo and in vitro. We confirmed different races have different tumor immune microenvironments. Immune microenvironment can influence and change the efficacy of immunotherapy for liver cancer patients.

The role of the stemness index-associated signature in the analysis of the tumorigenesis of liver cancer patients of different races.

Cancer stem cells (CSCs) are a subset of cancer cells with stem cell characteristics. The discovery of CSCs has opened a new era for cancer research. CSCs not only play a critical role in tumorigenesis, but also are responsible for the failure of cancer treatments. Here, we performed weighted gene co-expression network analysis (WGCNA) to identify key stemness genes and prognostic signatures using the data of an Asian liver cancer patient cohort and a White liver cancer patient cohort in The Cancer Genome Atlas (TCGA) database. To compare the difference in tumorigenesis between the Asian patients and the White patients, the prognostic value of the key genes from the Asian patients was evaluated in the White patient cohort and vice versa. We found that some key genes could predict the survival of the patients regardless of race. In addition, the key genes, NUCB2 and KLF4A, were selected from Asian patients and White patients, respectively, for further experimental validation. Knocking down NUCB2 could inhibit the activity of the AKT/mTOR signaling pathway and reverse the epithelial-mesenchymal transition (EMT) in liver cancer cells. We also confirmed that the knockdown of KLF4A suppressed ABCG2 activity and reduced the side population (SP) in liver cancer cells for the first time. Our results suggest that the stemness index is a useful method to identify key genes in tumorigenesis. Compared to the analysis for all patients, applying this index to the analysis of the patients of different races will provide more potential therapeutic targets for cancer treatment.

Effect of secretory DKK3 on circulating CD56bright natural killer cells in patients with liver cancer.

BACKGROUND: Liver cancer seriously threatens human health. Natural killer (NK) cells are an important part of the innate immune system and have strong anti-tumor ability. Immunotherapy based on NK cells has become a hot topic in the treatment of liver cancer. METHODS: In this study, we checked the serum DKK3 (sDKK3) and circulating CD56bright NK cells using ELISA and flow cytometry, respectively, in the blood of liver cancer patients. The effect on recombinant human DKK3 (rhDKK3) on CD56bright NK cells was analyzed in vitro. RESULTS: We found low levels of sDKK3 in liver cancer patients and a negative correlation between sDKK3 and circulating CD56bright NK cells. In addition, we found that DKK3 induced the differentiation and improved the cytotoxicity of CD56bright NK cells for the first time. It could be used as an agonist for NK cell-based immunotherapy. CONCLUSIONS: Improving the clinical efficacy of NK cells through DKK3 will become a new strategy for cancer immunotherapy.

Can CD147 work as a therapeutic target for tumors through COVID-19 infection?

In this review, we discussed an interesting case infected with "COVID-19" (Corona Virus Disease 2019). The patients with Hodgkin's lymphoma recovered after infection with COVID-19. It may be that COVID-19 activates the patient's immune system, or it may be a coincidence. COVID-19 spike protein can interact with CD147 and use it as an entry to invade host cells. CD147 is a partner of SLC3A2, which is the chaperone subunit of cystine/glutamate reverse transporter (system XC). The catalytic subunit of system XC is SLC7A11. SLC7A11 mediated cysteine uptake plays a key role in ferroptosis. Through literature review and data analysis, we suggest that CD147, as a new potential COVID-19 infection entry, may also lead to ferroptosis of host cells. Our hypothesis is that spike protein of COVID-19 induced ferroptosis in host cells via CD147/SLC3A2/SLC7A11 complex. This is another explanation for the cancer patient recovered after COVID-19 infection.

Both In Situ and Circulating SLC3A2 Could Be Used as Prognostic Markers for Human Lung Squamous Cell Carcinoma and Lung Adenocarcinoma.

SLC3A2, the heavy chain of the CD98 protein, is highly expressed in many cancers, including lung cancer. It can regulate the proliferation and the metastasis of cancer cells via the integrin signaling pathway. Liquid biopsy is a novel method for tumor diagnosis. The diagnostic or prognostic roles of serum SLC3A2 in lung cancer are still not clear. In this study, we analyzed SLC3A2 mRNA levels in human lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) using the TCGA database and serum SLC3A2 protein levels using ELISA. We confirmed high SLC3A2 levels in both the serum and tissue of LUAD and LUSC patients. Both serum and tissue SLC3A2 could be used as prognostic markers for overall LUAD and subgroups of LUSC patients. SLC3A2 induced tumorigenesis via the MEK/ERK signaling pathway in LUAD and LUSC cells.

Amino acid profiles in the tissue and serum of patients with liver cancer.

Most patients with liver cancer were found late and lost the chance of surgery. Liquid biopsy can monitor the risk of tumor recurrence and metastasis, quickly evaluate the curative effect of tumor treatment, and is conducive to early screening and auxiliary diagnosis of high-risk groups. Amino acid (AA) profiling has been used to the diagnosis and the prognosis for cancers. However, little was known about the profiles of AA of liver cancer. In this study, we used tRNA in Cancer database to analyze the AA levels in liver cancer tissues. Blood samples of patients with liver cancer were collected and analyzed using the automatic AA analyzer. We found that valine, isoleucine, and leucine were decreased significantly both in the plasma and the tumor tissues of patients with liver cancer. However, upregulation of methionine was observed in tissues and plasma of patients with liver cancer. Interestingly, tyrosine, and phenylalanine were decreased in tumor tissue but increased in the plasma of patients with liver cancer. This is the first report provided an overview of AA profile in both plasma and tissue for patients with liver cancer. AA levels can be used as diagnostic and prognostic markers of patients with liver cancer.

MICALL2 as a substrate of ubiquitinase TRIM21 regulates tumorigenesis of colorectal cancer.

BACKGROUND: Molecule interacting with CasL-like protein 2 (MICALL2) is believed to regulate cytoskeleton dynamics, tight junction formation, and neurite outgrowth. However, its biological role and the underlying mechanism in colorectal cancer (CRC) remain largely elusive. METHODS: qRT-PCR, Western blotting and immunohistochemistry assays were used to detect the expression levels of different genes. Next, mass spectrometry, co-immunoprecipitation and immunofluorescence staining were used to detect the interactions of proteins. Furthermore, MTT assay, colony formation assay, wound-healing assays and xenograft tumor models were performed to demonstrate the functions of MICALL2 in CRC. In addition, transcriptome sequencing and Western blotting were conducted to verify the mechanism of MICALL2 in CRC. RESULTS: We found that both mRNA and protein levels of MICALL2 are up-regulated in colorectal cancer tissues compared with non-tumor tissues and that its overexpression is closely correlated with poor prognosis. Ubiquitin E3 ligase Tripartite motif-containing protein 21 (TRIM21) mediated MICALL2 ubiquitination and proteasome-dependent degradation, negatively correlated with MICALL2 levels, and reversely regulated the tumorigenic activity of MICALL2 in CRC. Functional studies confirmed that MICALL2 promoted colorectal cancer cell growth and migration via the Wnt/ß-catenin signaling pathway. CONCLUSIONS: As a substrate of ubiquitinase TRIM21, MICALL2 enhances the growth and migration of colorectal cancer cells and activates the Wnt/ß-catenin signaling pathway. Video abstract.

Cancer Stem Cell Markers for Urinary Carcinoma.

Cancer stem cell (CSC) refers to cancer cells with stem cell properties, that is, they have the ability of "self-renewal" and "differentiation." Cancer stem cells exist in cancer cells and are the "culprit" of cancer recurrence and metastasis. It is difficult to be found because of its small amount, and it is difficult for anticancer drugs to produce effects on it. At present, the isolation and identification of cancer stem cells from many solid tumors are still quite difficult, mainly due to the lack of specific molecular markers of cancer stem cells. In this review, cancer stem cell surface markers and functional markers in urinary system were summarized. These markers can provide molecular targets for cancer therapy.

Cancer stem cell markers for liver cancer and pancreatic cancer.

Cancer stem cells (CSC) theory has ushered in a new era of cancer research. Tumor recurrence, metastasis and chemotherapy resistance are all related to the existence of cancer stem cells. Further understanding of tumor heterogeneity will contribute to targeted treatment. Liver cancer and pancreatic cancer are common digestive gland tumors with high lethality. This article reviews the identification and isolation of CSC markers in hepatocellular carcinoma and pancreatic cancer. The markers related signal pathways are involved in the occurrence and development of tumors, and have a significant impact on the proliferation, metastasis and invasion of cancer cells, which can be used as potential molecular therapeutic targets. This study will be helpful to understand cancer stem cell like cells.

MICAL1 inhibits colorectal cancer cell migration and proliferation by regulating the EGR1/ß-catenin signaling pathway.

MICAL1 has been reported to be involved in the malignant processes of several types of cancer cells, however, the roles of MICAL1 in colorectal cancer (CRC) have not been well-characterized. This study aims to investigate the cellular functions and molecular mechanisms of MICAL1 in CRC cells. Here, we found that both mRNA and protein levels of MICAL1 were down-regulated in colorectal cancer tissues compared with matched adjacent non-tumor tissues, and the expression level of MICAL1 was correlated with the metastatic status of colorectal cancer. Importantly, overexpression of MICAL1 significantly inhibited colorectal cancer cell migration and growth, and increased the level of E-cadherin and Occludin, and suppressed the expression level of Vimentin and N-cadherin; while silencing of MICAL1 promoted CRC cell migration and enhanced EMT. In addition, MICAL1 overexpression significantly inhibited the proliferation and growth of CRC in vitro and in vivo. Moreover, RNA sequencing and bioinformatics analysis identified that MICAL1 was closely correlated with "cell migration", "cell cycle" and "ß-catenin signaling" genesets. Mechanistically, overexpression of MICAL1 downregulated the mRNA level of EGR1 and ß-catenin, decreased the protein level and nuclear translocation of ß-catenin, and inhibited the transcriptions of ß-catenin downstream targets, c-myc and cyclin D1. The ectopic expression of EGR1 or ß-catenin can significantly block the MICAL1-mediated inhibitory effects. Collectively, MICAL1 is down-regulated in CRC, and plays an inhibitory role in the migration and growth of CRC cells by suppressing the ERG1/ß-catenin signaling pathway.

SOX4 induces drug resistance of colorectal cancer cells by downregulating CYLD through transcriptional activation of microRNA-17.

Exposure to high doses of anticancer drugs can induce the emergence of a subpopulation of weakly proliferative and drug-tolerant cells. Drug tolerance can reduce the benefits obtained from canonical treatment and reduce the survival rate of patients. Regulation of SRY-related HMG box transcription factor 4 (SOX4) has been proved to affect drug sensitivity. The current study aimed to explore the role of SOX4 in drug resistance of colorectal cancer (CRC) cells as well as the related molecular mechanisms. Expression patterns of SOX4, microRNA-17 (miR-17), and CYLD in both CRC tissues and cells were determined with their relationship analyzed by bioinformatics analysis, dual-luciferase reporter gene assay, and ChIP. Loss- and gain-function assays were performed to ascertain the effect of SOX4, miR-17, and CYLD on biological cellular processes and drug resistance to 5-FU. SOX4 and miR-17 were found to be highly expressed while CYLD was poorly expressed in CRC tissues and cells. Silencing of SOX4 resulted in the suppression of cellular proliferation, invasion, migration as well as a reduction in CRC drug resistance. Mechanically, CYLD was specifically targeted by miR-17, while SOX4 upregulated the expression of miR-17. Functionally, SOX4 triggered drug resistance of CRC cells to 5-FU through the miR-17/CYLD axis. Taken together, the key findings of the present study provides evidence suggesting that SOX4 elevates miR-17 to decrease CYLD, thus inducing chemotherapy resistance of CRC cells.

MiR-328-3p inhibits cell proliferation and metastasis in colorectal cancer by targeting Girdin and inhibiting the PI3K/Akt signaling pathway.

MiR-328-3p has been reported to be downregulated and serve as a tumor suppressor in several cancers. Previous studies only have reported the downregulation of miR-328-3p in CRC. However, the roles of miR-328-3p in CRC growth and metastasis were unknown. In this study, we demonstrated that miR-328-3p overexpression inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). The PI3K/Akt signaling pathway was also inactivated by miR-328-3p overexpression. MiR-328-3p knockdown showed the opposite effects. In addition, we confirmed that miR-328-3p directly bound to 3'UTR of Girdin and negatively regulated its expression. Girdin knockdown or treatment with PI3K inhibitor LY294002 blocked the effects of miR-328-3p inhibitor on cell proliferation, metastasis, and the PI3K/Akt signaling pathway. Moreover, pre-miR-328 decreased numbers of liver metastatic nodules, and reduced the levels of p-Akt, p-Girdin, and Girdin in metastatic tissues in liver. In conclusion, miR-328-3p may inhibit proliferation and metastasis of CRC cells by targeting Girdin and inactivating the PI3K/Akt signaling pathway. MiR-328-3p may be a novel target in cancer therapy.

MiR-346-5p promotes colorectal cancer cell proliferation in vitro and in vivo by targeting FBXL2 and activating the ß-catenin signaling pathway.

MiR-346-5p is overexpressed in several cancers, including colorectal cancer (CRC). However, the effects of miR-346-5p on CRC progression have not yet been clarified. In our study, miR-346-5p levels in four CRC cell lines and normal human colon epithelial cells were determined by real-time PCR. SW620 and HCT116 cells were selected and then transfected with miR-346-5p mimic, miR-346-5p inhibitor, or specific siRNAs targeting F-box/LRR-repeat protein 2 (FBXL2). Cell proliferation, cell cycle distribution and cell cycle regulators were examined by CCK-8 assay, flow cytometry, and western blot. The binding of miR-346-5p on 3' untranslated region (UTR) of FBXL2 were verified by dual-luciferase reporter assay. CRC cells were co-transfected with miR-346-5p inhibitor and siFBXL2 to investigate the involvement of FBXL2. Interaction of FBXL2 with forkhead box M1 (FoxM1) was examined by co-immunoprecipitation (Co-IP) assay. The effect of miR-346-5p knockdown on CRC tumorigenesis in vivo was investigated. Here, we found that miR-346-5p overexpression promoted, while miR-346-5p knockdown inhibited cell proliferation and G1-S transition. Inhibition of FBXL2 showed similar effects as miR-346-5p overexpression. Moreover, we verified that FBXL2 was a direct target of miR-346-5p. FBXL2 interacted with FoxM1, and then negatively regulated both FoxM1 and nuclear ß-catenin levels. Additionally, FBXL2 knockdown reversed the effects of miR-346-5p inhibitor. In xenograft models, miR-346-5p knockdown significantly inhibited tumor growth, increased FBXL2 expression, and downregulated the levels of FoxM1 and nuclear ß-catenin. In conclusion, miR-346-5p may promote CRC growth by targeting FBXL2 and activating the ß-catenin signaling pathway. MiR-346-5p may be a novel target in cancer therapy.