I kappa B kinase interacting protein as a promising biomarker in pan-cancer: A multi-omics analysis.

Background: Human chromosome 12 contains I kappa B kinase interacting protein (IKBIP) is also commonly known as IKIP. The involvement of IKBIP in the growth of tumors has only been discussed in a small number of publications. Purpose: To explore the role that IKBIP plays in the development of a wide variety of neoplasms, as well as the tumor immunological microenvironment. Methods: UALCAN, HPA, Genotype Tissue Expression, Cancer Genome Maps, and other datasets were used to analyze IKBIP expression. We thoroughly investigated the predictive importance of IKBIP in pan-cancer, clinical traits, and genetic anomalies. We studied whether there is a link between IKBIP and immune-related genes, microsatellite instability (MSI), and the incidence of tumor mutational burden (TMB). The link between immune cell infiltration and IKBIP expression was examined using data on immune cell infiltration from ImmuCellAI, TIMER2, and earlier studies. Finally, gene set enrichment analysis (GSEA) was performed to determine the signaling pathways associated with IKBIP. Results: IKBIP is highly expressed in most cancers and is negatively associated with the prognosis of several major cancer types. Furthermore, IKBIP expression was linked to TMB in 13 cancers and MSI in seven cancers. Additionally, IKBIP is associated with numerous immunological and cancer-promoting pathways. Simultaneously, various cancer types have unique tumor-infiltrating immune cell profiles. Conclusion: IKBIP has the potential to act as a pan-cancer oncogene and is crucial for both carcinogenesis and cancer immunity. Elevated IKBIP expression implies an immunosuppressive environment and may be used as a prognostic biomarker and therapeutic target.

PARP inhibitor olaparib enhances the efficacy of radiotherapy on XRCC2-deficient colorectal cancer cells.

The use of PARP inhibitors in combination with radiotherapy is a promising strategy to locally enhance DNA damage in tumors. Loss of XRCC2 compromises DNA damage repairs, and induced DNA damage burdens may increase the reliance on PARP-dependent DNA repairs of cancer cells to render cell susceptibility to PARP inhibitor therapy. Here we tested the hypothesis that XRCC2 loss sensitizes colorectal cancer (CRC) to PARP inhibitor in combination with radiotherapy (RT). We show that high levels of XRCC2 or PARP1 in LARC patients were significantly associated with poor overall survival (OS). Co-expression analyses found that low levels of PARP1 and XRCC2 were associated with better OS. Our in vitro experiments indicated that olaparib+IR led to reduced clonogenic survival, more DNA damage, and longer durations of cell cycle arrest and senescence in XRCC2-deficient cells relative to wild-type cells. Furthermore, our mouse xenograft experiments indicated that RT + olaparib had greater anti-tumor effects and led to long-term remission in mice with XRCC2-deficient tumors. These findings suggest that XRCC2-deficient CRC acquires high sensitivity to PARP inhibition after IR treatment and supports the clinical development for the use of olaparib as a radiosensitizer for treatment of XRCC2-deficient CRC.

The Effect of Ostracism on Adults' Materialism: The Roles of Security and Self-Construal.

With consumer culture becoming more prominent, the value of materialism is growing rapidly. This study explored the formation of materialism in adults, based on the temporal need-threat model of ostracism and the theory of materialistic values. Specifically, this study examined the link between ostracism and materialism from the perspective of security and the moderating role of self-construal in this process. A sample of 1,272 Chinese adults (M age = 35.90 ± 11.59, 47.2% male) was recruited to complete the Ostracism Experiences Scale, the Material Values Scale, the Security Questionnaire, and the Self-Construal Scale. The results showed that (1) ostracism positively predicted materialism in Chinese adults; (2) security partially mediated the relationship between ostracism and materialism; (3) and self-construal moderated this mediation model. The moderating effect of self-construal on the relationship between ostracism and security was significant. Specifically, the direct effect of ostracism on security was much stronger for adults with interdependent self-construal than for those with independent self-construal. However, self-construal had no significant moderating effect on the direct effect of ostracism on materialism. These findings suggest that ostracism may affect materialism by damaging adults' feelings of security, and independent self-construal can buffer the damage of ostracism on security.

Aberrant KIF23 expression is associated with adverse clinical outcome and promotes cellular malignant behavior through the Wnt/ß-catenin signaling pathway in Colorectal Cancer.

Purpose: The aim of the present study was to reveal the clinicopathological significance and prognostic role of kinesin family member 23 (KIF23) in colorectal cancer (CRC) and characterize its biological function and the underlying mechanisms. Methods: Bioinformatics analysis, immunohistochemistry, Western blot and qRT-PCR were utilized to investigate the expression of KIF23 in CRC tissues. The CCK-8 assay, wound healing assay and Matrigel assay were used to detect cell proliferation, migration and invasion in vitro. Western blot, immunofluorescence staining and cell function experiment were performed to explore the underlying mechanism. Results: The overexpression of KIF23 was associated with T stage, N stage, M stage and TNM stage, and CRC patients with high KIF23 expression had a worse prognosis. KIF23 knockdown inhibits CRC cells proliferation, migration and invasion in vitro. The mechanism study determined that KIF23 activates the Wnt/ß-catenin signaling pathway by promoting the nuclear translocation of ß-catenin to regulate the malignant behavior of CRC cells. Conclusion: These results suggest that KIF23 may act as a putative oncogene and a potential therapeutic target in CRC.

KIF20A Predicts Poor Survival of Patients and Promotes Colorectal Cancer Tumor Progression through the JAK/STAT3 Signaling Pathway.

Kinesin family member 20A (KIF20A) has been recently reported to be upregulated and associated with increased invasiveness and metastasis in several malignancies. However, the role of KIF20A in colorectal cancer (CRC) is still unclear. This study is aimed at investigating the potential roles of KIF20A in the development of CRC. The results of bioinformatics analysis, immunohistochemical staining, and Western blot analysis showed that KIF20A was overexpressed in CRC tissues compared with adjacent normal tissues. High expression of KIF20A in CRC tissues was associated with depth of invasion, lymphatic node metastasis, distant metastasis, and TNM stage. Moreover, the Kaplan-Meier survival analysis showed that CRC patients with high KIF20A expression had poor prognoses. Cox regression analysis revealed that KIF20A was an independent prognostic factor in patients with CRC. Further studies suggested that knockdown of KIF20A was able to reduce cell proliferation and migration by inhibiting the JAK/STAT3 pathway. Taken together, we propose that KIF20A plays a critical role in the tumorigenesis and tumor progression of colorectal cancer and could represent a potential therapeutic target for CRC.

miR­24 may be a negative regulator of menin in lung cancer.

The incidence of lung cancer in China increases annually, and effective targets for the diagnosis and treatment of lung cancer are urgently needed. miRNAs are currently considered to be involved in the regulation of tumor development and growth. miR­24 has been found to contribute to the development of several tumors. Menin is a key tumor suppressor gene, and its expression is generally low in lung cancer. The effects of miR­24 on the biological behavior of lung cancer cells were detected by MTT and Transwell assays. In the present study, miR­24 was found to be associated with menin, affecting the activity of the SMAD3 pathway in lung cancer by inhibiting menin expression. miR­24 may promote the growth and metastasis and inhibit the apoptosis of lung cancer cells by targeting menin. Therefore, the aim of the present study was to provide a new theoretical basis for the targeted therapy of lung cancer.

miR-646 is a key negative regulator of EGFR pathway in lung cancer.

BACKGROUND: As one of the leading cause of cancer-related deaths in the worldwide, lung cancer needs to be understood better. Nowadays, increasing point mutations of specific oncogenes are biomarkers used to predict the therapeutic effect of targeted therapy and lung cancer has entered the age of individual treatment. At present, many relevant researchers have suggested that EGFR is a biomarker used to predict the therapeutic effect of targeted therapy. A large number of evidence indicates that EGFR/Akt pathway plays important role in cancer growth and metastasis. AIM OF THE STUDY: In this paper, we found EGFR was a target of miR-646. RESULTS: Overexpression of miR-646 not only downregulated EGFR/Akt pathway, but also inhibited lung cancer cell proliferation and metastasis. At the same time, miR-646 was a prognosis factor for overall survival. CONCLUSION: Our finding could provide new insights into the molecular therapeutic of lung cancer.

Effects of PEMF on microcirculation and angiogenesis in a model of acute hindlimb ischemia in diabetic rats.

Hindlimb ischemia is a major complication of diabetic patients due to poor neovascularization. Therapy with pulsed electromagnetic fields (PEMF) can promote angiogenesis in ischemic lesions. However, the efficacy and therapeutic mechanisms of PEMF in diabetes-related hindlimb ischemia are unclear. Sprague-Dawley rats were injected with streptozocin to induce diabetes, and 10 weeks later diabetic rats were subjected to surgical induction of acute hindlimb ischemia. The rats were randomized and treated with PEMF, and the blood perfusion of individual rats was determined longitudinally by laser Doppler perfusion imaging (LDPI). The neovascular density was examined using immunofluorescent analysis of CD31 expression and alkaline phosphatase (AP) staining. The levels of VEGF, VEGFR, FGF-2, and FGFR1 expression, and ERK 1/2 and P38 phosphorylation in the muscles were characterized using enzyme-linked immunosorbent assay (ELISA) and Western blot assays. The values of LDPI in the PEMF-treated rats at 14 and 28 days post surgery were significantly greater than those in the controls, accompanied by significantly elevated levels of anti-CD31 and AP staining. The relative levels of FGF-2 and FGFR1, but not VEGF and VEGFR expression, and ERK1/2, but not P38 phosphorylation, in the muscles of the PEMF-treated rats were significantly higher than those in the controls. Our data indicated that PEMF enhanced acute hindlimb ischemia-related perfusion and angiogenesis, associated with up-regulating FGF-2 expression and activating the ERK1/2 pathway in diabetic rats. Therefore, PEMF may be valuable for the treatment of diabetic patients with ischemic injury.