A single RNA molecule links neuroblastoma to renal carcinoma

from biotechin.asia by Mohamad Moustafa Ali

The neuroblastoma-associated transcript 1 (NBAT1), previously known as CASC14, is a long noncoding RNA (lncRNA) molecule that is devoid of producing any functional protein. Initially, NBAT1 was found to have a plausible role in progression of neuroblastoma (NB) tumors, but more recently, a Chinese group from several universities published a paper in International Journal of Clinical and Experimental Pathology showing that NBAT1 is associated with poor prognosis in patients with clear cell renal cell carcinoma (ccRCC).

Although NB and ccRCC develop due to different molecular drivers that disturb normal cellular functions, it looks quite surprising that one RNA molecule maintains the same properties in promoting tumors in both cases. As a matter of fact, NB is a type of cancer that affects the sympathetic nervous system and arises from improper development and differentiation of neural crest cells. It is considered as the third most common tumor affecting infants and comprises around 7% of the total tumors observed in children.

The NB patients are categorized into many types; including patients with low-risk NB tumors and patients with high-risk tumors. The low-risk tumors are not associated with metastasis, rather they tend to differentiate into mature cells and respond to chemotherapy. On the contrary, high-risk tumors usually spread into different parts of the body and they show unfavorable clinical outcome due to their aggressive nature.


Kaplan-Meier overall survival curves of patients with ccRCC according to relative expression of NBAT-1. Patients with lower expression of NBAT-1 showed worse overall survival compared with patients with higher expression of NBAT-1 (P<0.05, log-rank test).

On the other hand, renal cell carcinoma (RCC) is responsible for almost 3% of all malignancies in adults, whereas ccRCC represents the major subtype of RCC. Unfortunately, most of RCC patients are administered to surgical treatment at later stages due to improper diagnosis of the complex symptoms; so nearly 30% of the patients develop metastatic tumors leading to lower survival time.

Few months ago, Gaurav Pandey and his colleagues at University of Gothenburg in Sweden published a research article in Cancer Cell journal pointing out to the role of NBAT1 in NB. Using state-of-the-art RNA-Seq technology, Pandey and his colleagues compared the RNA expression levels of high-risk and low-risk tumors derived from patients’ primary tumors. Their analysis indicated that NBAT1 tends to be expressed in lower levels in case of high-risk tumors compared to low-risk tumors. Further experiments on animals suggested an essential tumor suppression function of NBAT1. Enforced ectopic expression of NBAT1 induces cellular differentiation and restricts cellular proliferation by epigenetic silencing of common oncogenes. Statistical analysis in two different German and Swedish cohorts correlated lower expression of NBAT1 with lower survival time, while higher expression favors better prognosis.


The Risk-Associated Long Noncoding RNA NBAT-1 Controls Neuroblastoma Progression by Regulating Cell Proliferation and Neuronal Differentiation

The joint Chinese group was able to reproduce and verify the same observations in ccRCC patients. Using primary tumors derived from RCC patients, they reported lower expression of NBAT1 in more aggressive ccRCC tumors with advanced pathological features. Moreover, their experiments demonstrated the role of NBAT1 in prohibiting invasion and migration capacity of renal cancer cells. Although the current study in ccRCC has not discussed much about the molecular machinery that relates NBAT1 to other molecules in the cell, the data further confirm the possible use of NBAT1 as an independent prognostic marker to distinguish low-risk tumors from high-risk tumors.

For future perspectives, it would be worth to interrogate the common molecular networks that got affected upon abnormal expression of NBAT1 in NB and ccRCC; so that we can gain a comprehensive insight on molecular events that link diverse types of cancer.

Xue S, Li QW, Che JP, Guo Y, Yang FQ, Zheng JH. (2015) Decreased expression of long non-coding RNA NBAT-1 is associated with poor prognosis in patients with clear cell renal cell carcinoma. Int J Clin Exp Pathol 8(4):3765-3774. [article]


Pandey GK, Mitra S, Subhash S, Hertwig F, Kanduri M, Mishra K, Fransson S, Ganeshram A, Mondal T, Bandaru S, Ostensson M, Akyürek LM, Abrahamsson J, Pfeifer S, Larsson E, Shi L, Peng Z, Fischer M, Martinsson T, Hedborg F, Kogner P, Kanduri C. (2014) The risk-associated long noncoding RNA NBAT-1 controls neuroblastoma progression by regulating cell proliferation and neuronal differentiation. Cancer Cell 26(5):722-37. [abstract]

Source – biotechin.asia

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