Construction of a Diagnostic Model for Distinguishing Benign or Malignant Bone Cancer by Mining miRNA Expression Data.

Bone tumor is a kind of rare cancer, the location of which is mainly in bone tissue as well as cartilage tissue. Bone tumor is mainly classified into benign and malignant types. The survival rate of patients with bone tumors can be considerably improved by early detection, and the danger of amputation caused by bone tumors can be greatly reduced. In this study, we first screened the top 25% serum miRNAs with the greatest variance in patients with malignant and benign bone tumor and healthy individuals. The expression of serum miRNAs in patients with bone tumor was then examined using unsupervised clustering and PCA, and the results revealed that the overall expression of serum miRNAs was ineffective in distinguishing patients with benign/malignant bone tumors. Subsequently, we screened 19 miRNA biomarkers that could be used to determine the benign/malignant bone tumor of patients by LASSO logistic regression. These genes were validated using ROC curves. Results showed that there were 11 miRNAs that could accurately distinguish benign/malignant bone tumor alone. These 11 miRNAs were, namely, hsa-miR-192-5p, hsa-miR-137, hsa-miR-142-3p, hsa-miR-155-3p, hsa-miR-1205, hsa-miR-1273a, hsa-miR-3187-3p, hsa-miR-1255b-2-3p, hsa-miR-1288-5p, hsa-miR-6836-5p, and hsa-miR-6862-5p. Next, we established a diagnostic model using logistic regression and validated the diagnostic model using ROC curves; the result of which showed that the model had good diagnostic efficacy. Then, we also verified that the diagnostic model established by these 11 miRNAs could distinguish patients with benign/malignant bone tumor using unsupervised clustering as well as PCA. Finally, by using qPCR, we validated the expression of 11 miRNAs in the serum of patients with malignant and benign bone tumors, as well as healthy volunteers. The results were consistent with the trend of miRNAs expression in public databases. In summary, we examined the differential expression of serum miRNAs in individuals with benign and malignant bone tumors and discovered 11 miRNA biomarkers that could be utilized to discriminate between the two.

MiR-137 targets and regulates E2F7 to suppress progression of glioma cells.

INTRODUCTION: The paper aimed to explore the mechanism of miR-137 in modulating glioma. MATERIAL AND METHODS: qRT-PCR detected miR-137 and E2F7 mRNA expression in cells. The protein expression of E2F7 was measured using Western blot assay. Cell proliferation, scratch healing, transwell and programmed cell death assays were conducted to examine the influences of the genes on the biological function of glioma cells. The dual-luciferase assay verified the interaction between miR-137 and E2F7. RESULTS: MiR-137 was lowly expressed in glioma cells, and E2F7 was highly expressed. MiR-137 suppressed progression and promoted programmed cell death of glioma cells. MiR-137 could target and negatively regulate E2F7 expression to further accelerate programmed cell death of glioma cells. CONCLUSIONS: It was found that miR-137 could target E2F7 to restrain cell progression and accelerate programmed cell death of glioma cells, which is helpful to search for new molecular therapeutic targets for glioma.

Transcription Factor FXR Activates DHRS9 to Inhibit the Cell Oxidative Phosphorylation and Suppress Colon Cancer Progression.

Background: Colon cancer is a common gastrointestinal malignancy. It has been discovered that Farnesoid X receptor (FXR) plays an imperative regulatory role in multitype cancers in recent years. However, its regulatory mechanism in colon cancer has not been clearly explored. This study intended to explore the molecular regulatory mechanism of FXR and its downstream genes on the malignant progression of colon cancer. Methods: The mRNA and protein expression of FXR in colon cancer cells were measured by quantitative real-time polymerase chain reaction and Western blot. The effects of FXR on the biological function of colon cancer cells were measured by Cell Counting Kit-8, colony formation, and transwell assays. The downstream target gene of FXR was predicted by bioinformatics analysis and found to be associated with cellular oxidative phosphorylation. The binding relationship between FXR and its downstream gene dehydrogenase/reductase member 9 (DHRS9) was verified through luciferase reporter assay and chromatin immunoprecipitation assay. The changes of oxidative phosphorylation were detected by Western blot and oxygen consumption rate determination. The effect of FXR/DHRS9 axis on the malignant progression of colon cancer cells was further confirmed by rescue experiments. Results: FXR was underexpressed in colon cancer tissues and cells, and overexpressing FXR could repress the malignant behaviors of colon cancer cells. Besides, DHRS9 was a downstream gene of FXR, and FXR/DHRS9 inhibited the deterioration of colon cancer through inhibiting oxidative phosphorylation. Moreover, promoting FXR expression in colon cancer cells could partially reverse the biological function changes caused by silencing DHRS9 expression. Conclusion: FXR inhibited the oxidative phosphorylation and inhibited the malignant progression of colon cancer cells via targeting DHRS9.

miR-194-3p represses the docetaxel resistance in colon cancer by targeting KLK10.

BACKGROUND: Docetaxel (DCT) is widely adopted in chemotherapy for colon cancer (CC). However, DCT resistance can cause chemotherapy failure in CC. MicroRNAs (miRNAs) are key regulators of DCT resistance. Among them, miR-194-3p is a key tumor suppressor, but how it regulates DCT resistance has not been reported yet. This research explored the molecular mechanism of miR-194-3p/Kallikrein Related Peptidase 10 (KLK10) axis in regulating DCT resistance in CC. METHODS: The expression and targeting relationship of miR-194-3p and KLK10 was dug through bioinformatics analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was adopted to determine miR-194-3p level in CC cells. The over-expressed miR-194-3p cell group was constructed to ascertain the impacts of dysregulated miR-194-3p on DCT resistance. Through dual-luciferase assay, the targeting relationship of miR-194-3p and KLK10 was uncovered. Subsequently, the in vitro cellular experiments were performed to investigate the impacts of miR-194-3p/KLK10 axis on DCT resistance in CC cells. RESULTS: We noticed that miR-194-3p was notably down-regulated in CC cells. The over-expressed miR-194-3p restored the DCT sensitivity of SW620/DCT and SW480/DCT cells. Dual-luciferase assay suggested the targeting relationship of miR-194-3p and KLK10. Besides, miR-194-3p negatively regulated KLK10 expression level. In vitro cellular experiments further exposed that miR-194-3p could down-regulate KLK10, thereby attenuating DCT resistance in CC cells. SIGNIFICANCE: miR-194-3p could overcome DCT resistance in CC cells through negatively regulating KLK10. This finding offers a potential therapeutic target for clinical treatment of DCT chemoresistance in CC.

MiR-766-3p Suppresses Malignant Behaviors and Stimulates Apoptosis of Colon Cancer Cells via Targeting TGFBI.

BACKGROUND: MicroRNAs (miRNAs) can affect the progression of colon cancer cells. A variety of miRNAs, especially miR-766-3p, are proved to be abnormally expressed in colon cancer, but the molecular mechanism of miR-766-3p in this cancer has not yet been fully defined. METHODS: Differentially expressed genes in the TCGA-COAD dataset were searched through bioinformatics analysis. MiR-766-3p and TGFBI mRNA levels were measured by qRT-PCR. TGFBI protein expression was measured via Western blot. Targeting relation between miR-766-3p and TGFBI was investigated by dual-luciferase reporter gene assay. Cell proliferation, invasion migration, and apoptosis were detected by cell functional assays. RESULTS: MiR-766-3p was less expressed, while TGFBI was conspicuously highly expressed in colon cancer. MiR-766-3p high expression suppressed cell malignant behaviors and induced cell apoptosis in colon cancer. MiR-766-3p had a targeting relation with TGFBI verified by dual-luciferase assay. The cancer-suppressive impact of miR-766-3p overexpression was attenuated by overexpressing TGFBI. CONCLUSIONS: MiR-766-3p/TGFBI axis suppressed malignant behaviors and facilitated apoptosis of colon cancer cells. MiR-766-3p may be an underlying target for colon cancer.

Effect of chemokine CXCL14 on in vitro angiogenesis of human hepatocellular carcinoma cells.

The study was designed to investigate the effect of chemokine CXCL14 on in vitro angiogenesis of human hepatocellular carcinoma (HCC) cells. CXCL14 mRNA expression in HCC tissue samples and adjacent tissue samples was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). CXCL14 mRNA and protein expression in human normal hepatocyte HL-7702 and HCC cell line HepG2 were detected by qRT-PCR and western blot. In HepG2 cell line, the expression of vascular endothelial growth factor (VEGF) was detected by enzyme-linked immunosorbent assay method, cell viability was detected by CCK-8, cell proliferation was detected by colony formation assay, and cell migration as well as invasion ability was detected by Transwell assay. Moreover, human umbilical vein endothelial cell (HUVEC) tube formation assay was carried out to determine the cell ability of angiogenesis. Results showed that the overexpression of CXCL14 could inhibit angiogenesis, proliferation, migration, and invasion abilities of HCC cells.Highlights CXCL14 is lowly expressed in hepatocellular carcinoma tissues and cells. CXCL14 overexpression inhibits the angiogenesis of hepatocellular carcinoma cells. CXCL14 overexpression inhibits proliferation, invasion, and migration of hepatocellular carcinoma cells.

MiR-224-5p Targeting OCLN Promotes the Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma Cells.

A number of studies reported that miR-224-5p is involved in a variety of cancer-related cellular processes, yet its physiological role in clear cell renal cell carcinoma (ccRCC) remains unclear. In order to clarify the function of miR-224-5p in ccRCC, real-time quantitative-PCR was conducted to compare the expression of miR-224-5p in human normal renal tubular epithelial cell lines and ccRCC cell lines first, and a strikingly upregulated expression was observed in ccRCC cell lines. Inhibition of miR-224-5p expression by microRNA inhibitors could inhibit the proliferation, migration, and invasion of ccRCC cells. Besides, it was validated by dual-luciferase assay in which miR-224-5p directly targeted OCLN gene. The expression of OCLN was downregulated in ccRCC cells, and overexpression of miR-224-5p could inhibit the mRNA and protein expression levels of OCLN. Overexpression of OCLN could reduce the proliferation, migration, and invasion of ccRCC cells, while overexpressed miR-224-5p could partially reverse that inhibitory effect. Therefore, the promotive effect of miR-224-5p on the proliferation, invasion, and migration of ccRCC cell lines was at least partly due to the inhibition of OCLN expression. These findings highlighted the important function of miR-224-5p, which was promoting cell proliferation, migration, and invasion by downregulating OCLN, in the pathogenesis of ccRCC, and provided a potential treatment strategy.

miR-218-5p inhibits the malignant progression of glioma via targeting TCF12.

Several studies have shown the ability of transcription factor 12 (TCF12) to promote tumor malignant progression, but its function in glioma cells has not been fully elucidated. In this study, we analyzed the data from TCGA by bioinformatics and found that in glioma tissue, TCF12 was conspicuously highly expressed while miR-218-5p was significantly low-expressed. The downregulation of miR-218-5p was correlated with adverse prognosis in patients with glioma. miR-218-5p was found to be negatively associated with TCF12 by Pearson correlation analysis, and dual luciferase assay was employed to verify that miR-218-5p and TCF12 had a targeting relationship. qRT-PCR and Western blot assays were used to verify that the expression of TCF12 was regulated by its upstream regulator miR-218-5p. Moreover, cell experiments validated that overexpressed TCF12 could promote the proliferation, migration, and invasion of glioma cells and inhibit their apoptosis, whereas overexpressing miR-218-5p at the same time could reverse this phenomenon. Our study demonstrates the regulatory mechanism of the miR-218-5p/TCF12 axis in gliomas, which lays a foundation for searching for new therapeutic approaches for glioma.

Clinical research on the combined use of systemic chemotherapy and CT-guided radiofrequency ablation in treatment of lung cancer.

The purpose of this study is to describe the clinical efficacy and safety of the combined use of systemic chemotherapy and CT-guided radiofrequency ablation (RFA) in treatment of lung cancer. A panel of 256 patients with lung cancer who were admitted to our hospital from June 2017 to October 2019 were recruited. According to the treatment plan, the patients were divided into test group (n = 128) and control group (n = 128). Patients in the test group were treated by systemic chemotherapy combined with CT-guided RFA, while patients in the control group were given systemic chemotherapy only. After treatment, a comparative analysis was conducted in terms of clinical efficacy, level of tumor markers, and adverse reactions. Meanwhile, patients in the two groups were followed up for analysis of progression-free survival (PFS) and overall survival (OS). After treatment, the tumor objective response rate and disease control rate of patients in the test group were significantly higher than those in the control group. Besides, in patients of the test group, tumor markers, such as serum carcino-embryonic antigen, neuro-specific enolase, cytokeratin-19, and carbohydrate antigen-199, presented a remarkably lower level relative to those in the control group (p < 0.05). However, there was no significant difference observed with regard to the incidence of complications (p > 0.05). Additionally, patients in the test group were more likely to have better PFS and OS. Notably, we monitored that in the test group, superior clinical efficacy was achieved in patients with non-small cell lung cancer and lung adenocarcinoma relative to that in patients with small cell lung cancer and lung squamous cell carcinoma, respectively. The combined use of systemic chemotherapy and CT-guided RFA can produce good clinical efficacy in treatment of lung cancer. It is relatively safe and deserves promotion and application in clinic.

Exosomes Derived from Cancer-Associated Fibroblasts Regulate Cell Progression in Clear-Cell Renal-Cell Carcinoma.

BACKGROUNDS: Exosomes from multiple sources function as regulatory factors in progression of various tumors. However, studies on the impact of exosomes from cancer-associated fibroblasts (CAFs) on tumor-cell proliferation, migration, invasion, and cycle regulation in clear-cell renal-cell carcinoma (ccRCC) are still lacking. METHODS: A Western blot assay was performed to test the exosome-related marker protein level in exosomes derived from CAFs and normal fibroblasts (NFs). A confocal microscope was utilized to observe the internalization of CAF- and NF-derived exosomes after coculturing with cancer cells. MTT, EdU, colony formation, and transwell assays were conducted to detect progression of cancer cells incubated with CAF-derived exosomes. A Western blot assay was also conducted to test expression levels of metastasis-associated proteins. Changes in cell apoptosis and cell cycle were measured by flow cytometry. RESULTS: Expression of CAF-derived exosome-related marker proteins was higher than that from NFs. Exosomes derived from CAFs and NFs could enter into cancer cells smoothly and be internalized by cancer cells. After cancer cells were cocultured with CAF-derived exosomes, cell proliferation, migration, and invasion were notably enhanced, and cell apoptosis was reduced. Moreover, expression of fibronectin, N-cadherin, vimentin, MMP9, and MMP2 in cancer cells increased, while E-cadherin was decreased. Besides, the proportion of cancer cells in the S phase increased. CONCLUSION: CAF-derived exosomes are internalized into ccRCC cells and promote the progression of ccRCC.

miR-181a-2-3p Stimulates Gastric Cancer Progression via Targeting MYLK.

Background: The abnormal expression of miRNAs facilitates tumorigenesis and development. miR-181a-2-3p is up-regulated in various cancers, yet its mechanism in gastric cancer (GC) remains elusive. Objective: To understand mechanism of miR-181a-2-3p stimulating GC cell progression via targeting Myosin Light Chain Kinase (MYLK) expression. Methods: Downstream genes of miRNA of interest were predicted in TargetScan and miRTarBase. qRT-PCR and western blot were applied to assess miR-181a-2-3p and MYLK expression in GC cells and normal cells. Dual-luciferase and RIP assays were completed to assess binding of miR-181a-2-3p and MYLK. Cell Counting Kit-8 (CCK-8) assay was conducted for detecting viability of AGS and SNU-1 cells, while Transwell tested migratory and invasive abilities of cells. Nude mouse transplantation tumor experiment was performed to assay tumor growth in vivo. Results: miR-181a-2-3p was notably increased in human GC cell lines, while MYLK was remarkably down-regulated. RIP and dual-luciferase assay disclosed that miR-181a-2-3p targeted MYLK and repressed MYLK. Forced miR-181a-2-3p expression fostered GC cell proliferation, invasion, migration, and fostered tumor growth in vivo. Promoting effect of miR-181a-2-3p on GC cells was reversed when miR-181a-2-3p and MYLK were simultaneously overexpressed. Conclusion: miR-181a-2-3p facilitated GC cell progression by targeting MYLK, and it may be a pivotal prognostic biomarker in investigating molecular mechanism of GC.

MiR-490-5p Restrains Progression of Gastric cancer through DTL Repression.

Gastric cancer (GC) accounts for a main cause of cancer-related deaths. This study sought for molecular mechanism of miR-490-5p/DTL axis in affecting GC progression, thus bringing new hope for treatment of GC. Expression data of differentially expressed miRNAs and mRNAs in GC tissue from TCGA database were analyzed. MiR-490-5p and DTL mRNA expression levels in GC were evaluated with qRT-PCR. Cell viability was confirmed with CCK-8 method. Cell cycle distribution and apoptosis were analyzed with flow cytometry. Cell migratory and invasive potential was proved with Transwell assay. The targeted relationship between DTL and miR-490-5p was analyzed with dual-luciferase assay. The results indicated a decreased miR-490-5p level in GC cells. MiR-490-5p upregulation hampered proliferation, migration, invasion and promote cell apoptosis. DTL was the target of and inversely associated with miR-490-5p, and it could remarkably induce the carcinogenesis of GC. MiR-490-5p mediated GC cell progression by DTL repression. In conclusion, miR-490-5p and DTL may be valuable in diagnosis and treatment for GC.

Identifying 13 Hub Genes Associated with Progression and Prognosis of Hepatocellular Carcinoma with Weighted Gene Co-Expression Network Analysis.

Hepatocellular carcinoma (HCC) is a type of common cancer, often accompanied by tumor recurrence and metastasis after surgery with poor prognosis. Therefore, searching into potential biomarkers that can effectively predict the prognosis and progression of HCC is crucial. In this study, we identified 1,981 differentially expressed genes (DEGs) using mRNA expression profiles from the TCGA-LIHC dataset. Subsequently, weighted gene co-expression network analysis found that the turquoise module closely associated with the pathological grade and clinical stage of HCC was identified. Then, from the key genes in the turquoise module and protein-protein interaction network analysis, 13 hub genes significantly related to the prognosis of HCC were screened. Through co-expression and functional enrichment analyses, these 13 hub genes were found to play an important role in mitosis. Finally, we evaluated the relationship between these hub genes and overall survival and disease-free survival through survival analysis. The result indicated that HCC patients with high hub gene expression had a poorer prognosis than HCC patients with low expression. Receiver operating characteristic curves showed that each hub gene could predict the prognosis of HCC patients. In summary, a total of 13 hub genes were identified that play an important role in the progression of HCC, which can be used as potential biomarkers for HCC patients.

miR-15b-3p promotes the malignant progression of endometrial cancer cells through targeting KLF2.

Human endometrial cancer is one of the most common malignant tumors in women with an increased incidence by years. The biological function of miR-15b-3p in endometrial cancer is still unclear. Therefore, this study explores the expression and potential mechanism of miR-15b-3p in endometrial cancer, providing a novel theory basis for targeted therapy. Herein, differentially expressed miRNAs and mRNAs in endometrial cancer were determined by bioinformatics analysis. qRT-PCR measured expression of miRNAs and mRNAs. The protein expression of mRNA in cells was determined by western blot. MTT, wound healing, and Transwell assays evaluated the biological behavior of cells. Dual luciferase assay validated the targeted relationship between target miRNA and mRNA. miR-15b-3p was highly expressed in endometrial cancer, and overexpression of miR-15b-3p promoted the malignant progression of endometrial cancer cells. KLF2 was a downstream target of miR-15b-3p, and overexpression of KLF2 reversed the facilitation of miR-15b-3p on endometrial cancer cells. miR-15b-3p promoted the proliferation, migration, and invasion of endometrial cancer cells by targeting KLF2, which made miR-15b-3p a potential diagnostic factor and new molecular therapeutic target for endometrial cancer.

MiR-92a-3p Promotes the Malignant Progression of Hepatocellular Carcinoma by Mediating the PI3K/AKT/mTOR Signaling Pathway.

BACKGROUND: As one of the most common cancers globally, hepatocellular carcinoma (HCC) usually has a poor prognosis. Many HCC patients are usually diagnosed at advanced stages. Therefore, new potential biomarkers for the diagnosis and prognosis of HCC are urgently needed. More and more studies have shown that miR-92a-3p can regulate the occurrence and development of various cancers, but its clinical significance and molecular mechanism in HCC are still elusive. Here, we tried to clarify the regulatory mechanism of miR-92a-3p in HCC. METHODS: In this study, we conducted qRT-PCR and revealed that miR-92a-3p was notably upregulated in HCC cells. MTT, flow cytometry, wound healing, Transwell invasion assays and western blot were conducted to uncover that overexpressed miR-92a-3p could boost the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells while inhibiting cell apoptosis. In addition, the proteins associated with the PI3K/AKT/mTOR pathway were also detected by western blot. RESULTS: It was suggested that miR-92a-3p could activate the PI3K/AKT/mTOR signaling pathway. CONCLUSION: These results suggest that miR-92a-3p plays a tumor-promoting role in HCC and may be a potential biomarker for the diagnosis and prognosis of HCC.

Delivery of miR-224-5p by Exosomes from Cancer-Associated Fibroblasts Potentiates Progression of Clear Cell Renal Cell Carcinoma.

OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma. Cancer-associated fibroblasts (CAFs) as the primary components of cancer stroma can affect tumor progression by secreting exosomes, while exosomes are carriers for proteins, nucleic acids, and other agents that responsible for delivery of biological information. Given this, exosomes derived from CAFs are emerging as promising biomarkers in clinical cancer diagnosis. Nevertheless, their role in clear cell renal cell carcinoma (ccRCC) remains poorly understood. METHODS: Here, we separated fibroblasts from ccRCC tissue, extracted exosomes, observed their morphology, and detected the expression of exosome marker proteins including Hsp70, CD9, and CD63. In the meantime, we labeled exosomes and performed coculture experiment to verify the delivery of miR-224-5p from CAFs to 769-P cells with exosomes as a carrier, so as to clarify the effect of CAF-derived exosomes on ccRCC cell malignant behaviors, as well as to discuss how miR-224-5p involves in above regulation. RESULTS: Transmission electron microscopy was firstly applied, and it was noted that the exosomes we isolated were in normal range. Besides, Western blot also confirmed the presence of exosome marker proteins Hsp70, CD9, and CD63. Furthermore, coculture experiments were performed and the CAF-derived exosomes were observed to be able to facilitate the malignant behaviors of ccRCC cells, and the exosomal miR-224-5p could be internalized by ccRCC cells to participate in regulation of cell proliferation, migration, invasion, and apoptosis. CONCLUSION: To sum up, miR-224-5p can enter ccRCC cells via CAF-derived exosomes, in turn, promoting the malignant behaviors of ccRCC cells, which indicates that miR-224-5p has the potential severing as a therapeutic target for ccRCC.

MiR-433-3p restrains the proliferation, migration and invasion of glioma cells via targeting SMC4.

OBJECTIVE: Glioma is a common primary malignant brain tumor characterized by high mortality and poor prognosis. The purpose of this study is to explore the molecular mechanism underlying glioma, aiming to provide a new target for the treatment of glioma to improve the prognosis of patients. METHODS: The differentially expressed genes and regulatory axis affecting the prognosis of glioma were identified with bioinformatics analysis, and the expression of miR-433-3p and SMC4 mRNA was detected with qRT-PCR. The expression of SMC4 and epithelial-mesenchymal transition (EMT)-associated proteins were detected with western blot. The targeting relationship between miR-433-3p and SMC4 was verified with dual-luciferase reporter gene assay. The proliferative ability of glioma cells was detected with CCK-8 assay, while the migration and invasion of glioma cells were detected with Transwell assay. RESULTS: We found that the expression of SMC4 was significantly up-regulated in glioma, showing that SMC4 was an unfavorable factor for prognosis and could promote the progression of cancer cells. Its upstream regulator miR-433-3p was significantly down-regulated in glioma, which inhibited the development of cancer cells. Moreover, miR-433-3p could target to inhibit the expression of SMC4. Rescue assay showed that miR-433-3p could affect the development of glioma by regulating the expression of SMC4. CONCLUSION: Our data demonstrate for the first time that SMC4 is a direct target of miR-433-3p, and elucidate the molecular mechanism by which miR-433-3p inhibits the malignant progression of glioma by targeting and down-regulating the expression of SMC4.

TP53 rs28934571 polymorphism increases the prognostic risk in hepatocellular carcinoma.

Aim: Hepatocellular carcinoma (HCC) is considered to be the third leading cause of cancer death. The homologous gene of TP53 is significant in the occurrence and development of cancer. This study explored the relationship between TP53 rs28934571 polymorphism and HCC risk in Guangxi, China. Materials & methods: We first screened the association through bioinformatics. Additionally, a case-control study was performed to further verify the relationship between gene polymorphism and HCC risk after collecting clinical characteristics. Results: Results showed that allele A on TP53 rs28934571 was a risk factor for HCC and mutation from C to A on TP53 rs28934571 would increase the risk of poor prognosis of HCC. Conclusion: Therefore, the study concluded that TP53 rs28934571 may become a diagnostic indicator in judging the prognosis of HCC.

A nine-gene signature to improve prognosis prediction of colon carcinoma.

This study aims to establish a gene model that can robustly and effectively predict the prognosis of colon carcinoma patients via bioinformatics. Data along with clinical information in GSE39582 Series Matrix were firstly downloaded from Gene Expression Omnibus (GEO) database. Next, differentially expressed genes (DEGs) were obtained through "edgeR" analysis. Finally, a risk predication model was established through a series of regression analyses, and then prognostic performance of the model was comprehensively evaluated though Kaplan-Meier and receiver operating characteristic (ROC) analysis. Gene set enrichment analysis (GSEA) was further performed. Totally, 846 DEGs were obtained by analyzing the gene expression data in GSE39582 dataset. A 9-gene signature-based risk predication model was established via regression analyses, and the model-based risk score was formulated as: Riskscore = (-0.1214) * TNFRSF11A + (-0.2617) * TMEM97 + (-0.1041) * LGR5 + 0.0973 * KLK10 + 0.1655 * HOXB8 + 0.227 * FKBP10 + (-0.1312) * CXCL13 + (-0.1316) * CXCL10 + 0.2593 * CD36. Kaplan-Meier curve showed that colon carcinoma patients in the high-risk group had a lower survival rate. GSEA showed that high-risk group and low-risk group displayed significant difference in biological pathways including ECM RECEPTOR INTERACTION. Besides, correlation analysis between the riskscore of the model and clinical features of patients revealed that the model could effectively predict the prognosis of patients in different ages (age>65, age<65) and stages (tumor_stage I/II, tumor_stage III/IV, T3&T4, N0&N1, N2&N3, M0). This study provides a robust model for the prognosis prediction of colon carcinoma, and lays a basis for researching the molecular mechanism underlying the development of colon carcinoma.

MiR-452-5p mediates the proliferation, migration and invasion of hepatocellular carcinoma cells via targeting COLEC10.

Objective: This study explored the potential function of miR-452-5p in hepatocellular carcinoma (HCC) and clarified the mechanism underlying HCC progression. Materials & methods: Real-time quantitative PCR was used to detect miR-452-5p and COLEC10 mRNA expression in HCC, western blot was performed to test COLEC10 protein expression. The regulatory mechanism of miR-452-5p/COLEC10 in HCC cells was explored using CCK-8, wound healing assay, Transwell and dual-luciferase reporter assay. Results: MiR-452-5p was greatly upregulated in HCC cells, and it served as an oncogene playing an active role in HCC cell proliferation, migration and invasion. COLEC10 was identified as the target of miR-452-5p in HCC attenuating the promoting effect of miR-452-5p on HCC cells upon overexpression. Conclusion: MiR-452-5p can promote the progression of HCC via targeting COLEC10.