Our study aimed to investigate the effects of lncRNA LOXL1‐AS1/miR‐let‐7a‐5p/EGFR‐axis on prostate cancer (PCa) progression. Microarray analysis was conducted to determine differentially expressed lncRNAs and mRNAs. Gene Set Enrichment analysis was implemented for verification of dys‐regulated signaling pathways between DU‐145 cells and doxorubicin‐resistant prostate cancer DU‐145 cells. Relative expression of lncRNA LOXL1‐AS1 in doxorubicin‐resistant prostate cancer DU‐145 cells was analyzed by qRT‐PCR. CCK‐8 assay and flow cytometry analysis were employed to detect cell proliferation and apoptosis, respectively. Cell migration was performed by transwell assay. Furthermore, targeted relationships between lncRNA LOXL1‐AS1 and miR‐let‐7a‐5p, as well as miR‐let‐7a‐5p and EGFR were predicted using bioinformatics analysis and validated by dual‐luciferase reporter gene assay. Besides, tumor xenograft assay was utilized for verification of the roles of LOXL1‐AS1 in PCa progression in vivo. Microarray analysis showed that lncRNA LOXL1‐AS1 and EGFR were both downregulated, while miR‐let‐7a‐5p was upregulated in doxorubicin‐resistant prostate cancer DU‐145 cells. MiR‐let‐7a‐5p could target both lncRNA LOXL1‐AS1 and EGFR to affect PCa progression. Upregulation of lncRNA LOXL1‐AS1 promoted cell proliferation and migration, while suppressed cell apoptosis. Besides, it was further confirmed that EGFR was downregulated in drug‐resistant PCa cells and negatively correlated with miR‐let‐7a‐5p. Tumor xenograft assay verified that silence of lncRNA LOXL1‐AS1 inhibited the tumor growth in vivo in DU‐145 cells. Our results demonstrated that the lncRNALOXL1‐AS1/miR‐let‐7a‐5p/EGFR axis significantly affected proliferation, migration, and apoptosis of drug‐resistant DU‐145 Cells, which may provide us with a potential treatment strategy for drug‐resistant PCa patients. © 2019 IUBMB Life, 2019

Objective: To identify the expression of kinetochore scaffold 1 ( KNL1) in colorectal tumor tissues and to clarify the role of this gene in the proliferation capability of colorectal cancer cells. Methods: A total of 108 paired colorectal tumor and normal tissue samples were collected from patients with colorectal cancer and subjected to quantitative polymerase chain reaction and immunohistochemistry analyses. Expression levels of KNL1 mRNA and protein were compared between tumor and normal tissues, and KNL1 levels were evaluated in relation to the patients’ tumor differentiation, sex, lymph node metastasis, TNM stage, infiltration depth, age, and tumor location. Survival curves were also constructed and compared between patients with tumor samples with and without KLN1 protein expression. KNL1 was under-expressed in colorectal cancer cells in vitro using lentiviral transfection with short hairpin RNA, and its function was evaluated by proliferation, colony-formation, and apoptosis assays. Expression levels of BUB1 protein were also compared between tumor and normal tissues, and the correlation between KNL1 expression and BUB1 expression in colorectal cancer tissues was examined. Results: KNL1 mRNA and protein were both highly expressed in colorectal tumor tissues compared with paired normal tissues. KNL1 downregulation significantly inhibited colorectal cancer cell proliferation and colony formation, and promoted apoptosis. KNL1 protein expression was significantly associated with tumor differentiation, but not with sex, lymph node metastasis, TNM stage, infiltration depth, age, or tumor location. KNL1 protein expression was also significantly associated with poorer survival. Moreover, there was a significant correlation between KNL1 and BUB1 in colorectal cancer tissues. Conclusions: KNL1 plays an effective role in decreasing apoptosis and promoting the proliferation of colorectal cancer cells, suggesting that its inhibition may represent a promising therapeutic approach in patients with colorectal cancer.

We performed a meta‐analysis to evaluate the effect of body mass index on surgical site wound infection, mortality, and postoperative hospital stay in subjects undergoing possibly curative surgery for colorectal cancer. A systematic literature search up to March 2022 was performed and 2247 subjects with possibly curative surgery for colorectal cancer at the baseline of the studies; 2889 of them were obese, and 9358 were non‐obese. Odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) were calculated to assess the effect of body mass index on surgical site wound infection, mortality, and postoperative hospital stay in subjects undergoing possibly curative surgery for colorectal cancer using the dichotomous or contentious methods with a random or fixed‐effect model. The obese subjects had a significantly higher surgical site wound infection after colorectal surgery (OR, 1.87; 95% CI, 1.62‐2.15, P < .001), and higher mortality (OR, 1.58; 95% CI, 1.07‐2.32, P = .02) in subjects with possibly curative surgery for colorectal cancer compared with non‐obese. However, obese did not show any significant difference in postoperative hospital stay (MD, 0.81; 95% CI, −0.030 to 1.92, P = .15) compared with non‐obese in subjects with possibly curative surgery for colorectal cancer. The obese subjects had a significantly higher surgical site wound infection after colorectal surgery, higher mortality, and no significant difference in postoperative hospital stay compared with non‐obese in subjects with possibly curative surgery for colorectal cancer. The analysis of outcomes should be with caution because of the low number of studies in certain comparisons.

Objective Thymidine Phosphorylase (TYMP) gene was of potential significance in the process of colorectal cancer (CRC) development and played an important role in capecitabine metabolism. This study was to identify the association between TYMP polymorphism and prognosis of postoperative patients with CRC who received capecitabine-based adjuvant chemotherapy. Methods A total of 218 patients with CRC who were treated with surgical resection and capecitabine-based adjuvant chemotherapy were included in this study retrospectively. Peripheral blood and peripheral blood mononuclear cell (PBMC) specimen of the patients were collected for the genotyping of TYMP polymorphism and TYMP mRNA expression, respectively. Univariate analysis of genotypes and prognosis was carried out by Kaplan–Meier survival analysis, Cox regression analysis was adopted in multivariate analysis. The mRNA expression of TYMP according to genotype status was analyzed using non-parameter test. Results Prevalence of rs11479 in TYMP among the 218 patients exhibited that minor allele frequency of rs11479 was 0.20 (GG 141 cases, GA 68 cases and AA 9 cases), which was in accordance with Hardy-Weinberg equilibrium ( P =0.825). Association analysis suggested that the median disease-free survival (DFS) of patients with GG genotype and GA/AA genotype was 3.1 and 6.1 years, respectively ( P =0.004). Furthermore, the median overall survival of patients with GG genotype and GA/AA genotype was 5.0 and 7.0 years, respectively ( P =0.033). Multivariate Cox regression analysis exhibited that rs11479 polymorphism was an independent factor for DFS (HR = 1.64, P =0.009). Additionally, of the 65 PBMC specimens, mRNA expression results indicated that patients with GA/AA genotypes conferred significantly higher mRNA expression of TYMP than that of patients with GG genotype ( P <0.001). Conclusion Polymorphism rs11479 in TYMP gene might predict the prognosis of patients with CRC who received capecitabine-based adjuvant chemotherapy through mediation of the mRNA expression of TYMP . The conclusion of this study should be validated in prospective clinical trials subsequently.

Background/Aims: Colorectal cancer (CRC) is the third most common malignant tumour worldwide and the second leading cause of cancer-related deaths. Commonly, 5'-aminolevulinic acid synthase1 (ALAS1) is the rate-limiting enzyme for haem biosynthesis. Recent studies have shown that ALAS1 is involved in a number of cellular functions and has significant effects on non-small cell lung cancer (NSCLC). However, current concepts of disease pathogenesis fail to fully explain the role of ALAS1 expression and biological functions in CRC. Materials and Methods: A total of 67 paired tumour tissues and adjacent colorectal tissues were used to detect ALAS1 levels and further analyse the correlation between ALAS1 expression levels and clinical features. Using HCT116 cell lines, we studied the impact of ALAS1 on biological function by knocking down or inhibiting ALAS1. Results: We found an increase in the levels of ALAS1 in cancer tissues compared to adjacent colorectal tissues. The increase in ALAS1 expression was closely related to the invasion depth, N staging and tumour size of CRC patients. The proliferation and metastasis of CRC cells could be inhibited by suppressing ALAS1. Conclusions: The abnormal expression of ALAS1 is closely related to the proliferation and metastasis of CRC cells, suggesting that ALAS1 may be a novel therapeutic target for the treatment of CRC.

31Background: To identify the expression of KNL1 in colorectal tumor tissues and to 32 clarify the function of this gene on the proliferation capability of colorectal cancer 33 cells. 34 Methods: Thirty-six pairs of colorectal tumor and normal tissue were collected and 35 subjected to quantitative PCR analysis. KNL1 was under-expressed using lentiviral 36 transfection, and the function of KNL1 was evaluated by proliferation assay, colony 37 formation and apoptosis assay.38 Results: KNL1 was highly expressed in colorectal tumor tissues. KNL1 39 downregulation inhibited colorectal cancer cell proliferation and promoted 40 apoptosis. 41 Conclusions: KNL1 plays an effective role in decreasing the apoptosis and promoting 42 the proliferation of colorectal cancer cells. 43 44 45Colorectal carcinoma (CRC) has been reported to be the second deadliest cancer 1-4 . 46Although the overall morbidity and mortality of CRC has decreased in recent decades, 47 there has been a considerable increase in patients <50 years of age 4-6 . Additionally, 48 the 5-year survival of CRC is only 14% as the tumor is often not completely 49 resectable 5, 6 . Despite advances in therapeutic strategies and diagnostic approaches, 50 the prognoses for patients with CRC typically remain poor 7 . Therefore, there is an 51 urgent need to develop new CRC treatment approaches. We previously reported the 52 effects of D40 cloning on chromosome 15 8 , and D40 was characterized to be a 53 cancer-related gene that is primarily expressed in the testis under normal conditions, 54 but is widely expressed in primary tumors of various origins as well as assorted 55 cancer cell lines 9, 10 . A previous study has reported the mutual translocation of 56 AF15q14 with the MLL (Mixed lineage leukemia) gene in acute myeloid leukemia 11 . 57AF15q14, a human gene on chromosome 15, was also identical to the D40 gene 8 . 58 Furthermore, D40 expression has been reported to be associated with the pathological 59 features of primary lung tumors, such as degree of differentiation, and patients' 60 Tianliang Bai et al: Effect of KNL1 on the proliferation and apoptosis smoking history 10 . In a study of the testes, D40 was found to be expressed in 61 pre-acrosomes and spermatocytes 12 . A follow up study revealed that blinkin, a type of 62 kinetochore protein in the mitotic machinery was identical to KNL1. In addition to 63 binding of KNL1/blinkin with Ndc80 and Mis12 complexes, of which the KMN 64 network is comprised, binding is also observed between KNL1/blinkin and other 65 proteins, including tubulin, spindle assembly checkpoint (SAC) proteins BubR1 and 66 Bub1, and Protein Phosphatase 1 13-17 . Such binding suggests that KNL1/blinkin has 67 crucial impacts on kinetochore formation in terms of the connection between spindles 68 and chromosomes, as well as the regulation of SAC 13-18 . 69 Primary microcephaly (MCPH) is a rare congenital neurodevelopment disorder 70 that is known to have autosomal recessive features 19, 20 . Due to different levels of 71 mental retardation, ...

Japonica-specific markers are crucial for the analysis of genetic diversity, population structure, evolutionary traits, and genome-wide association study (GWAS) of japonica germplasm accessions. This study developed 402 insertion–deletion (InDel) polymorphic markers based on the re-sequencing of four japonica rice landraces and three japonica rice cultivars. These InDel markers were uniformly distributed across 12 rice chromosomes with high polymorphism and good amplification specificity. The average density of InDel markers on each chromosome was 0.95 Mb per locus. On the basis of these InDel markers, genetic diversity analyses and GWASs for 12 salt-tolerance-related traits were performed using 182 japonica rice accessions. In total, 1204 allelic variants were detected, with an average of 3.00 alleles and 2.10 effective alleles per locus. Based on population structure analysis, 182 japonica rice accessions were divided into four subgroups. The GWAS analyses revealed a total of 14 salt-tolerance-related InDels, which were located on chromosomes 1–5, 9, 10, and 12. Twenty-eight allelic loci were identified, explaining 6.83% to 11.22% of the phenotypic variance. Haplotype analysis detected six InDel markers associated with salt-tolerance-related traits that were significantly different (p < 0.05) or highly significantly different (p < 0.01) among different haplotypes. These markers can be utilized for the molecular identification of salt-tolerant rice germplasm accessions.

Soil salinity seriously restricts rice growth, development, and production globally. Chlorophyll fluorescence and ion content reflect the level of injury and resistance of rice under salt stress. To understand the differences in the response mechanisms of japonica rice with varying degrees of salt tolerance, we analyzed the chlorophyll fluorescence characteristics and ion homeostasis of 12 japonica rice germplasm accessions by comprehensive evaluation of phenotype, haplotype, and expression of salt tolerance-related genes. The results revealed that salt-sensitive accessions were rapidly affected by the damage due to salinity. Salt tolerance score (STS) and relative chlorophyll relative content (RSPAD) were extremely significantly reduced (p&lt;0.01), and chlorophyll fluorescence and ion homeostasis were influenced by various degrees under salt stress. The STS, RSPAD, and five chlorophyll fluorescence parameters of salt-tolerant accessions (STA) were significantly higher than that of salt-sensitive accessions (SSA). Principal component analysis (PCA) with 13 indices suggested three principal components (PCs), with a cumulative contribution rate of 90.254%, which were used to screen Huangluo (typical salt-tolerant germplasm) and Shanfuliya (typical salt-sensitive germplasm) based on the comprehensive evaluation D-value (DCI). The expression characteristics of chlorophyll fluorescence genes (OsABCI7 and OsHCF222) and ion transporter protein genes (OsHKT1;5, OsHKT2;1, OsHAK21, OsAKT2, OsNHX1, and OsSOS1) were analyzed. The expressions of these genes were higher in Huangluo than in Shanfuliya under salt stress. Haplotype analysis revealed four key variations associated with salt tolerance, including an SNP (+1605 bp) within OsABCI7 exon, an SSR (−1231 bp) within OsHAK21 promoter, an indel site at OsNHX1 promoter (−822 bp), and an SNP (−1866 bp) within OsAKT2 promoter. Variation in OsABCI7 protein structure and differential expression of these three ion-transporter genes may contribute to the differential response of japonica rice to salt stress.