Non-small-cell lung cancer (NSCLC) represents the most common deadly disease. Emerging evidences suggest that abnormal epigenetic modulation via mRNAs and
microRNAs (
miRNAs) might be involved in the
tumorigenesis. To explore novel therapeutic target of NSCLC, a more detailed mRNAs and
miRNA expression profiling study is needed. High-quality total
RNA including
miRNA was isolated from NSCLC tissue and para-
carcinoma tissue and used for
RNA and small
RNA sequencing. Results were analyzed bioinformatically and validated using quantitative real-time (qRT)-PCR. A total of 3530 genes (1977 up-regulated and 1553 down-regulated) and 211
miRNAs (171 up-regulated and 30 down-regulated) were differentially expressed (DE) in NSCLC tissue versus adjacent normal tissues. Furthermore, 157 novel
miRNAs were predicted in our samples. Of these, 918 significant
miRNA-
mRNA pairs were identified, consisting of 100
miRNAs and 443 mRNAs. Gene ontology analysis revealed that most of the target genes were enriched in the terms of plasma membrane, binding, and multiple biological-molecular signaling processes. Pathway analysis of these
miRNA signatures highlights their critical roles in calcium signaling pathway. Using qRT-PCR, the expression of several DE genes (KRAS and RBM5) and
miRNAs (miR-1-5p, let-7b-5p, miR-21-5p, miR-1290, miR-149-5p, chr8_28846, chrX_31594, and chr9_29897) were confirmed. The integrative analysis based on
mRNA and
miRNA profiling may provide more potential molecular for the
tumorigenesis and development of NSCLC.