Colorectal cancer (CRC) is already the third common cause of cancer in terms of incidence and the second most deadly cancer in the world. Due to the changes in lifestyle and everyday diet, the incidence of CRC has been increased. CRC is a complex and molecularly heterogeneous disease (1, 2). Multiple genetic and epigenetic alterations occur in the transition from normal colonic mucosa to invasive adenocarcinomas (3). Despite advances in diagnosis and treatment of CRC, the recurrence and mortality still remain high, with 5-year survival rate less than 65% (4–6).
Long non-coding RNAs (lncRNAs) are defined as RNA transcripts with more than 200 nucleotides in length, while do not harbors any open reading frame, and thus have no protein-coding potential. LncRNAs are expressed in many loci of the genome and modulate gene expression in the nucleus and the cytoplasm (7, 8). They are involved in a large range of biological processes as gene-regulatory components. Also, the oncogenic or tumor suppressor roles of these molecules have been demonstrated (9). Moreover emerging studies have revealed that aberrant/dysregulated expression of lncRNAs have linked to the pathogenesis of cancer (10, 11). LncRNAs may be involved in carcinogenesis and the progression of tumors through a variety of mechanisms by interfering in diverse cell signaling pathways (12–14).
Due to their critical functions in cancer development, they have been attracted as the potential therapeutic targets for cancer gene therapy (11, 15).
One such lncRNA gene is maternally expressed gene 3 -MEG3 (also known as gene trap locus 2 (GTL2)), located in chromosome 14q32. MEG3 RNA is expressed in many normal tissues, while aberrantly expressed in multiple cancers such as cervical cancer, prostate cancer, bladder cancer, and CRC (16–19). MEG3 has been found as tumor suppressor and inhibits cancer cell proliferation, migration, and induce apoptosis in vitro and in vivo by stimulating the p53-dependent transcription (20, 21).
Moreover, lincRNA-Regulator of Reprogramming (linc-ROR) is located at chromosome 18q21.31. It was initially reported as an important modulator in the reprogramming differentiated cells to induced pluripotent stem cells (iPSCs) (22). Growing evidence demonstrated that its aberrant expression and oncogenic role in many types of malignant carcinomas including breast cancer, pancreatic cancer, gallbladder cancer nasopharyngeal carcinoma and CRC (23–25).
Further research elucidated that the linc-ROR could negatively regulate the p53 and act as inhibiting the p53‐mediated cell cycle and apoptosis (23, 26). Therefore, a strategy to overcome the resistance to p53-dependent apoptosis is to target the regulators that influenced the expression of the p53. Here, we aimed to explore the simultaneous effect of linc-ROR silencing and increasing expression of MEG3 on the survival of HCT116 cells. The cell response to the transcription expression level of p53 in response to this recombinant vector was evaluated.