Chandra Vishal, Kim Jong Joo, Mittal Balraj, Rai Rajani
Vishal Chandra, Department of Obstetrics and Gynecology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States.
World J Gastroenterol. 2016 Feb 7;22(5):1787-99. doi: 10.3748/wjg.v22.i5.1787.
Gallbladder cancer (GBC) is infrequent but most lethal biliary tract malignancy characterized by an advanced stage diagnosis and poor survival rates attributed to absence of specific symptoms and effective treatment options. These necessitate development of early prognostic/predictive markers and novel therapeutic interventions. MicroRNAs (miRNAs) are small, non-coding RNA molecules that play a key role in tumor biology by functioning like tumor suppressor- or onco- genes and their aberrant expression are associated with the pathogenesis of several neoplasms with overwhelming clinical implications. Since miRNA signature is tissue specific, here, we focused on current data concerning the miRNAs aberrations in GBC pathogenesis. In GBC, miRNAs with tumor suppressor activity (miR-135-5p, miR-335, miR-34a, miR-26a, miR-146b-5p, Mir-218-5p, miR-1, miR-145, mir-130a) were found downregulated, while those with oncogenic property (miR-20a, miR-182, mir-155) were upregulated. The expression profile of miRNAs was significantly associated with GBC prognosis and prediction, and forced over-expression/ inhibition of these miRNAs was shown to affect tumor growth and development. Further, differential expression of miRNAs in the blood samples of GBC patients suggest miRNAs as promising noninvasive biomarker. Thus, miRNAs represent potential candidate for GBC management, though many hurdles need to be overcome before miRNAs therapy can be clinically applied to GBC prevention and treatment.
胆囊癌(GBC)并不常见,但却是最致命的胆道恶性肿瘤,其特征为诊断时已处于晚期,且由于缺乏特异性症状和有效的治疗方案,生存率较低。因此,需要开发早期预后/预测标志物和新型治疗干预措施。微小RNA(miRNA)是小的非编码RNA分子,通过发挥肿瘤抑制基因或癌基因的作用在肿瘤生物学中起关键作用,其异常表达与几种肿瘤的发病机制相关,具有重大的临床意义。由于miRNA特征具有组织特异性,在此,我们聚焦于目前有关GBC发病机制中miRNA异常的相关数据。在GBC中,具有肿瘤抑制活性的miRNA(miR-135-5p、miR-335、miR-34a、miR-26a、miR-146b-5p、Mir-218-5p、miR-1、miR-145、mir-130a)被发现表达下调,而具有致癌特性的miRNA(miR-20a、miR-182、mir-155)则表达上调。miRNA的表达谱与GBC的预后和预测显著相关,并且这些miRNA的强制过表达/抑制显示会影响肿瘤的生长和发展。此外,GBC患者血液样本中miRNA的差异表达表明miRNA是有前景的非侵入性生物标志物。因此,miRNA是GBC治疗的潜在候选物,尽管在miRNA疗法能够临床应用于GBC的预防和治疗之前,还需要克服许多障碍。