ABSTRACT
Long non-coding RNA (lncRNA) KCNQ1 and opposite strand/antisense transcript 1 (KCNQ1OT1) have been validated to be carcinogenic in several cancers. However, the role of KCNQ1OT1 in regulating the malignant biological behavior and radiotherapy resistance of cervical cancer (CC) remains largely unknown. Quantitative real time-polymerase chain reaction (qRT-PCR) was carried out to detect KCNQ1OT1 and miR-491-5p expression in CC tissues and cells. Pyruvate kinase M1/2 (PKM2) expression was detected by Western blot. CC cell proliferation, movement, migration and invasion were monitored by CCK-8, scratch healing and Transwell assay, respectively. The CC cell colony survival was detected by colony formation assay under different doses of radiation. Dual luciferase reporter gene assay, pull-down assay and RIP assay were employed to verify the targeting relationship between KCNQ1OT1, miR-491-5p and PKM2. In this study, KCNQ1OT1 was significantly up-regulated in CC patient cancerous tissues and cell lines, and its high expression was significantly related to tumor volume increase and poor differentiation. KCNQ1OT1 overexpression significantly promoted CC cell proliferation, metastasis and radioresistance. On the contrary, KCNQ1OT1 knockdown compared to the control group inhibited the above biological behavior of CC cells. The underlying mechanism suggested that KCNQ1OT1 promoted progression and radioresistance of CC by modulating the miR-491-5p/PKM2 axis. In conclusion, KCNQ1OT1 enhances CC cell progression through the miR-491-5p/PKM2 axis.
ABSTRACT
AIMS: To investigate the possibility of reducing excess sludge production in activated sludge processes by the addition of chemical uncouplers to greatly dissociate anabolism from catabolism. METHODS AND RESULTS: Ortho-chlorophenol (oCP), 2,4-dichlorophenol (DCP), 3,3',4',5-tetrachlorosalicylanilide (TCS), para-dinitrophenol (pNP) and 2,4-dinitrophenol (DNP) were chosen for short-term tests for their ability to reduce sludge yield by shaking bottle test. The most effective chemicals, DNP and pNP, together with TCS were tested for various uncoupler concentrations and biomass concentrations. TCS was tested in a lab-scale completely mixed activated sludge batch culture. The model (demonstrated by Liu) was verified with experimental data in completely mixed activated sludge batch test, but was inconsistent with the results from the shaking bottle batch test. The observed growth yield (Yobs) decreased with increasing of the ratio of initial uncoupler concentration to initial biomass concentration (Cu/X0). CONCLUSIONS: We suggest that the uncouplers oCP, DCP, TCS, pNP and DNP can cause a significant decrease in sludge production, the metabolism of which can explain the decline in sludge yield. SIGNIFICANCE AND IMPACT OF THE STUDY: The real strength of chemical uncoupler imposing on biomass should be Cu/X0, not initial uncoupler concentration (Cu) alone. Chemical uncouplers can be used to develop the activated sludge processes for minimizing excess sludge production.