Reduced miR-433 expression is associated with advanced stages and early relapse of colorectal cancer and restored miR-433 expression suppresses the migration, invasion and proliferation of tumor cells in vitro and in nude mice.

The expression of microRNA (miR-433) is altered in various types of human cancer. The present study analyzed the prognostic and biological value of miR-433 expression in colorectal cancer using reverse transcription-quantitative polymerase chain reaction in 125 colorectal tissue specimens (including a test cohort of 40 cases of paired colorectal cancer and adjacent normal mucosae and a confirmation cohort of 85 cases of stage I-III colorectal cancer). In vitro and nude mouse xenograft experiments were subsequently used to assess the effects of miR-433 expression on the regulation of colorectal cancer cell proliferation, adhesion, migration, and invasion. The data indicated that miR-433 expression was significantly downregulated in colorectal cancer tissues in the test and confirmation patient cohorts and that low miR-433 expression was associated with advanced tumor stage and early relapse. Furthermore, the restoration of miR-433 expression was able to significantly inhibit the proliferation of tumor cells by inducing G1-S cell cycle arrest, suppressing cyclinD1 and CDK4 expression, and markedly inhibited the migratory and invasive capacities of tumor cells in vitro. The restoration of miR-433 expression or liposome-based delivery of miR-433 mimics suppressed the growth of colorectal cancer cell xenografts in nude mice. In conclusion, miR-433 may be a putative tumor suppressor in colorectal cancer, and the detection of low miR-433 expression will be investigated in further studies as a putative biomarker for the detection of early relapse in patients with colorectal cancer.

miR-206 enhances nasopharyngeal carcinoma radiosensitivity by targeting IGF1.

Radioresistance remains a major problem in nasopharyngeal carcinoma (NPC) treatment. However, the underlying molecular mechanisms of NPC radioresistance remain poorly understood. The present study aimed to investigate the potential role and mechanism of miR-206 in NPC radioresistance. We observed that miR-206 was down-regulated in radioresistant NPC cells. Furthermore, restoration of miR-206 in CNE2-IR cells suppressed enhanced radiosensitivity of NPC cells. In contrast, inhibition of miR-206 in CNE2 cells reduced the radiosensitivity. We also found that miR-206 directly targeted IGF1 and inhibited the PI3K/AKT pathway. Our data demonstrate that miR-206 sensitizes NPC cell to irradiation by targeting IGF1, highlighting the therapeutic potential of miR-206 in NPC radiosensitization.

[Antipyretic effect of moxibustion at different temperatures and its relationship with the activity of temperature sensitive neurons in thermotaxic center].

OBJECTIVE: To discover the central mechanisms of antipyretic effect of moxibustion and its relationship with the acupoint sensor so as to provide the scientific evidence for "the treatment of heat syndrome with moxibustion". METHODS: Eighteen New Zealand Rabbits were randomly assigned into three groups, named group A (modeling with intravenous injection of Endotoxin), group B (moxibustion at 40 degrees C after Endotoxin injection) and group C (moxibustion at 48 degrees C after Endotoxin injection), 6 rabbits in each one. The experiment was undergoing in the condition of muscular relaxation and artificial respiration for the animals. The spotlight moxibustion at constant temperature was applied to "Zhiyang" (GV 9). The discharge of heat sensitive neurons (HSNs) at the preoptic region and anterior hypothalamus (POAH) was taken as the index. The impacts of the treatment on HSNs were observed in each group. RESULTS AND CONCLUSION: Moxibustion had significant antagonism to the pyrogen on its inhibition to the activity of HSNs in the thermotaxic center. As a result, the antipyretic effect was obtained. It is concluded that the effective result of moxibustion is achieved by stimulating polymodal receptors of acupoints.

[Effects of strong and weak electroacupuncture on endotoxin-induced changes of electrical activities of heat-sensitive neurons in preoptic area and anterior hypothalamus in rabbits].

OBJECTIVE: To observe the effects of weak and strong electroacupuncture (EA) on endotoxin (ET) thermolysis-induced changes of discharges of neurons in the preoptic region and anterior hypothalamus (PO-AH) so as to explore its underlying mechanism in antipyretic and thermolytic actions and its relation to the receptive system of acupoints. METHODS: Eighteen New Zealand rabbits were randomly divided into ET group, ET + weak-EA group and ET + strong-EA group. Extracellular discharges of the PO-AH neurons were recorded by using tungsten microelectrodes. A "U"-shape stainless steel tube was implanted in the region (P0.4-A4.4, L0.5-1.7) crossing the hypothalamus for changing local temperature by perfusion of cool (25 degrees C) or warm (41 degrees C) solution in order to distinguish the heat sensitive neurons (HSN), cold sensitive neurons (CSN) and insensitve neurons to temperature changes. Intravenous injection of endotoxin (25 EU/rabbit) was given to rabbits to induce increase of tempe rature. EA (8 Hz, wave width 0.1 ms, weak stimulation: 4.5 V, strong stimulation: 25 V) was applied to bilateral "Yongquan" (KI 1) for observing changes of firing rates of HSN in PO-AH. RESULTS: Compared with the basal values of firing rates of PO-AH neurons in each group, the average changing ratios of both ET and ET + weak-EA groups decreased significantly from 55-60 min on in ET group and from 40-45 min on in ET + weak-EA group after intravenous injection of ET (P<0.05), suggesting no marked effect of weak EA for preventing discharges of PO-AH neurons from decrease. While in ET + strong-EA group, the firing rates of HSN of PO-AH kept stable after injection of ET during EA and after cease of EA (P>0.05 vs basal value), suggesting that strong EA could antagonize ET thermolysis-induced decrease of firing rates of PO-AH neurons. CONCLUSION: Stronger EA stimulation of KI1 can antagonize ET thermolysis-induced effect on electrical activities of PO-AH HSN, which may be initiated by the activation of the high-threshold thin nerve fibers in the acupoint region.