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Background Breast cancer anti-estrogen resistance 4 (BCAR4) is closely associated with colorectal cancer (CRC) initiation and propagation. However, the mechanisms underlying BCAR4 function in colon cancer remains largely unknown. In this study, we hypothesized that BCAR4 could regulate colon cancer stem/initiating cells (CSC) function and further facilitates the colon cancer progression. Methods qRT-PCR was used to examine the expression of BCAR4 and various CSC markers. FACS, acetaldehyde dehydrogenase (ALDH) activity and western blot assays were applicable to test the expression of CSC markers. CCK8, tumorsphere formation and transwell assays were adopted to examine the capacity of CRC cells proliferation, self-renewal and migration. Pull down assay was used to test the interaction between BCAR4 and miR-665. Luciferase reporter assay was used to examine the interaction of miR-665 and activators of transcription (STAT3). In vivo tumor xenograft study was used to verify the malignancy of CRC cells with inhibition of BCAR4. Results Breast cancer anti-estrogen resistance 4 was highly expressed in both CRC cells and stem/initiating cells. In addition, overexpression of BCAR4 facilitated the maintenance of ALDH positive cells (a type of cancer stem/initiating cells) stemness and promoted ALDH+ cells proliferation and migration. Inhibition of BCAR4 restricted ALDH+ cells proliferation and migration. We further proved that miR-665 was the target of BCAR4 and subsequently activated signal transducers and STAT3 signaling which is an important pathway in cancer stem cells self-renewal. Conclusions Breast cancer anti-estrogen resistance 4 promotes the CRC cells stemness through targeting to miR-665/STAT3 signaling and identification of the BCAR4 in CRC stem cells provides a new insight into CRC diagnosis, treatment, prognosis and next-step translational investigations.

BCAR4 (Breast Cancer Anti-Estrogen Resistance 4) is a long noncoding RNA that was identified as an oncogene in breast cancer. In our research, we found that the expression level of BCAR4 was upregulated in colon cancer tissues compared to paired normal tissues. What's more, higher BCAR4 expression was correlated with lower survival rate in patients with colon cancer. Mechanistically, we showed that BCAR4 activated Wnt/β-catenin signaling in colon cancer by protecting β-catenin from degradation. We also showed that BCAR4 overexpression promoted cell proliferation and migration in colon cancer. However, silencing BCAR4 inhibited cell growth and promoted apoptosis. Besides, BCAR4 knockdown decreased tumor growth in vivo. These findings indicate that BCAR4 facilitated colon cancer progression by enhancing cell proliferation and inhibiting apoptosis via BCAR4/β-catenin axis. BCAR4 may be a useful new target for treatment of patients with colon cancer.

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Salmonella is an important cause of foodborne diseases. This study was undertaken to investigate the prevalence, serotype distribution, antimicrobial resistance, virulence genes, and genetic diversity of Salmonella isolates recovered from fresh duck meat obtained from retail markets in Southern China. In total, 365 samples of fresh duck meat were collected from retail markets in six different cities of Guangdong Province between May 2017 and April 2019. High levels of Salmonella contamination were detected in duck meat (151/365, 41.4%). Twenty-six different Salmonella serotypes were identified: S. Corvallis (n = 25, 16.6%), S. Kentucky (n = 22, 14.6%) and S. Agona (n = 20, 13.3%) were the most prevalent serotypes. All isolates were resistant to at least one antibiotic and 133 (88.1%) isolates exhibited multidrug resistance (MDR). Most (86.1%) Salmonella isolates carried seven classes of virulence-associated genes. This study showed the diversity of Salmonella serotypes and genotypes and the high prevalence of MDR isolates carrying multiple virulence-associated genes among isolates from duck meat obtained from retail markets in Southern China. Isolates from different districts had similar pulsed-field gel electrophoresis (PFGE) patterns indicating that circulating foodborne Salmonella constitutes a potential public health issue across different districts.