geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

let-7b/g silencing activates AKT signaling to promote gastric carcinogenesis


, : let-7b/g silencing activates AKT signaling to promote gastric carcinogenesis. Journal of Translational Medicine 12(): 281-281

Aberrant AKT activation contributes to gastric cancer cell survival and chemotherapy resistance, however its regulation is poorly understood. microRNAs have been established to be important regulators in gastric carcinogenesis. Here, we showed the functional role and putative target of let-7b and let-7g (let-7b/g) in gastric carcinogenesis. The expression of let-7b/g in gastric cancer cell lines and primary tumors were evaluated by miRNA qRT-PCR. The putative target gene of let-7b/g was explored by TargetScan followed by further validation. Functional analyses including MTT proliferation, monolayer colony formation, cell invasion assays and in vivo study were performed in both ectopic expression and knockdown approaches. let-7b/g was found down-regulated in gastric cancer and its downregulation was associated with poor survival and correlated with lymph node metastasis. let-7b/g inhibited AKT2 expression by directly binding to its 3'UTR, reduced p-AKT (S473) activation and suppressed expression of the downstream effector pS6. AKT2 mRNA expression showed negative correlation with the expression of let-7b/g in primary tumors. Short interfering RNA (siRNA) mediated knockdown of AKT2 phenocopied the tumor-suppressive effects of let-7b/g. Moreover, AKT2 re-expression partly abrogated the growth-inhibitory effect of let-7b/g. In conclusion, our findings reveal decreased let-7b/g contributes to aberrant AKT activation in gastric tumorigenesis and provide a potential therapeutic strategy for gastric cancer.

US$19.90

PMID: 25288334

DOI: 10.1186/s12967-014-0281-3


Other references

Chandler, M.J.; Zhang, J.; Qin, C.; Yuan, Y.; Foreman, R.D., 2000: Intrapericardiac injections of algogenic chemicals excite primate C1-C2 spinothalamic tract neurons. Extracellular potentials of 38 C1-C2 spinothalamic tract (STT) neurons in anesthetized monkeys (Macaca fascicularis) were examined for responses to intrapericardiac injections of an algogenic chemical mixture (adenosine, 10(-3) M; bradykinin, pros...

Ramus, S.J.; Harrington, P.A.; Pye, C.; Peock, S.; Cook, M.R.; Cox, M.J.; Jacobs, I.J.; DiCioccio, R.A.; Whittemore, A.S.; Piver, M.Steven.; EMBRACE.E.ston, D.F.; Ponder, B.A.J.; Pharoah, P.D.P.; Gayther, S.A., 2007: Screening for the BRCA1-ins6kbEx13 mutation: potential for misdiagnosis. Mutation in brief #964. Online. Misdiagnosis of a germline mutation associated with an inherited disease syndrome can have serious implications for the clinical management of patients. A false negative diagnosis (mutation missed by genetic screening) limits decision making about...

Sanner, B., 2005: Obstructive sleep apnea -- an underrated cardiovascular risk factor. Deutsche Medizinische Wochenschrift 130(49): 2817-2817

D.Pereira, B.V., 1952: Clinical evolution of cystic pneumatosis of the intestine. Portugal Medico 36(10): 542-548

Sandel, B.R.; Broadfoot, A.L.; Shemansky, D.E., 1977: Microchannel plate life tests. We have investigated the manner in which the gain of a microchannel plate (MCP) changes as the plate is operated at moderate output currents. We find that the total charge per unit area Q (C-cm(-2)) extracted from the MCP is the relevant quantity...

Lahdesmaki P., 1987: Characterization of low molecular weight acidic peptides in the leaves of trifolium repens and phaseolus vulgaris. Leaf extracts from Trifolium repens and Phaseolus vulgaris contained several acidic low-molecular weight peptides, the fractions of which were obtained among the most acidic amino acids in an automatic amino acid analyzer and purified further with...

Bernard S.Robbins M.D., 1943: Wishful thinking. Trying to figure out what's going on inside the mind of an adolescent can be challenging, to say the least. A new study shows that simply asking them what they wish for could be eye-opening.

Trivedi, D.; Singh, S.; Hooke, R., 2008: Conflict resolution: a guide for the foundation year doctor. British Journal of Hospital Medicine 69(8): M114-M115

Elektorowicz, C.; Lawniczak, K.; Zielina, J., 1963: Endothelioma pleurae. A male patient aged 33 with endothelioma pleurae is reported. The onset of the disease was atypical and exsudative serous pleuritis was diagnosed. After some month the tomogrammes revealed tumors starting from the chest walls, the region of the di...

Montenegro Alvaro; Hetherington Renee; Eby Michael; Weaver Andrew J., 2006: Modelling pre-historic transoceanic crossings into the Americas. A method for simulating vessel movement in an oceanic setting is described and used to provide temporal and spatial constraints to potential pre-historic transoceanic crossings into the Americas. The technique is based on current and wind output f...