Transcriptional analysis of hnRNPA0, A1, A2, B1, and A3 in lung cancer cell lines in response to acidosis, hypoxia, and serum deprivation conditions

ABSTRACT

The ribonucleoproteins (hnRNPs) have important roles in multiple aspects of nucleic acid metabolism and in the regulation of different cellular processes. Abnormal expression of hnRNPs has been reported in several types of cancer including lung, pancreatic, and gastric carcinomas. Heterogenous tumor cell populations generate a tumor microenvironment that can present normoxic, hypoxic, or acidic regions. The analysis of hnRNP transcriptional responses considering the changing nature of the tumor microenvironment is important to understand tumor cell survival under stress conditions. We analyzed the transcriptional response of hnRNPA0, A1, A2, B1, and A3 in lung tumor cell lines under acidosis, hypoxia, and serum deprivation conditions. We used qRT-PCR to obtain a relative quantification of the hnRNPA/B transcript levels. We found that the hnRNPA2 transcript was the most abundant, followed by B1, A0, and A1. Expression of hnRNPA3 was the lowest, although its transcript levels were the most constant. hnRNPA/B transcript levels in lung tumor cell lines responded to changes in the microenvironment; however, hnRNPB1 transcript levels relative to hnRNPA2 expression did no change in all tested stress conditions, indicating that the alternative splicing between these isoforms was constant. hnRNPA1, A2, and B1 transcript levels were upregulated under serum deprivation conditions; possibly to promote a migration phenotype. Our data provide new insights into the transcriptional responses of ribonucleoproteins that might favor tumor cell survival and migration.

KEYWORDS :

• alternative splicing
• qRT-PCR
• ribonucleoprotein
• tumor microenvironment