RESUMO
In this study, to investigate whether endoplastic reticulum (ER) stress correlated with FOXM1 in colorectal cancer, we analysed the mRNA levels of FOXM1 and ER stress markers HSPA5 and spliced XBP1 by qRT-PCR. FOXM1 mRNA levels were found to positively correlate with HSPA5 in colorectal cancer. However, no significant correlation between FOXM1 and spliced XBP1 mRNA levels was found. Theses results suggested the positive correlation between FOXM1 and HSPA5 in colorectal cancer was not associated with ER stress. Next, we provided evidences that FOXM1 promoted HSPA5 transcription by directly binding to and stimulating HSPA5 promoter. Moreover, a FOXM1-binding site mapped between -1019 and -1012 bp of the proximal HSPA5 promoter was identified. In addition, we found that enhancement of cell migration and invasion by FOXM1 was significantly attenuated by depletion of HSPA5 in colorectal cancer cell. Furthermore, FOXM1 triggered colorectal cancer cell migration and invasion was involved in activities of cell-surface HSPA5. Lastly, our results suggested FOXM1 facilitated the activities and expressions of MMP2 and 9 associated with cell-surface HSPA5 in colorectal cancer cells. Moreover, statistically significant positive correlations between FOXM1 and MMP2 mRNA expression, between HSPA5 and MMP2 were found in colorectal cancer tissue specimens. Together, our results suggested that FOXM1-HSPA5 signaling might be considered as a novel molecular target for designing novel therapeutic regimen to control colorectal cancer metastasis and progression.
Assuntos
Neoplasias Colorretais/patologia , Proteína Forkhead Box M1/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Proteínas de Choque Térmico/metabolismo , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Chaperona BiP do Retículo Endoplasmático , Proteína Forkhead Box M1/genética , Proteínas de Choque Térmico/genética , Humanos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Ativação TranscricionalRESUMO
State-of-the-art endoscopy systems require electronics allowing for real-time, bidirectional data transfer. Proposed are 2.4-GHz low-power transceiver analog front-end circuits for bidirectional high data rate wireless telemetry in medical endoscopy applications. The prototype integrates a low-IF receiver analog front-end [low noise amplifier (LNA), double balanced down-converter, bandpass-filtered automatic gain controlled (AGC) loop and amplitude-shift keying (ASK) demodulator], and a direct up-conversion transmitter analog front-end [20-MHz IF phase-locked loop (PLL) with well-defined amplitude control circuit, ASK modulator, up-converter, and power amplifier] on a single chip together with an internal radio frequency oscillator and local oscillating (LO) buffers. Design tradeoffs have been made over the boundaries of the different building blocks to optimize the overall system performance. All building blocks feature circuit topologies that enable comfortable operation at low power consumption. The circuits have been implemented in a 0.25-microm CMOS process. The measured sensitivity of the receiver analog front-end is -70 dBm with a data rate of 256 kbps, and the measured output power of the transmitter analog front-end could achieve -23 dBm with a data rate of 1 Mbps. The integrated circuit consumes a current of 6 mA in receiver mode and 5.6 mA in transmitter mode with a power supply of 2.5 V. This paper shows the feasibility of achieving the analog performance required by the wireless endoscopy capsule system in 0.25 microm CMOS.
