LncRNAs are transcribed RNA molecules over 200 bases in length that lack significant protein-coding potential. There are correlations between lncRNAs and DNA-binding proteins, like chromatin-modifying complexes [15, 18]. These transcripts play critical roles in physiological processes . LncRNAs were initially considered to be spurious transcriptional noise. However, in the past few years, thousands of lncRNAs were recognized, and the functional roles of them in epigenetics have been argued [13, 16]. LncRNAs, functioning as regulatory agents, have been defined for various complex cellular processes, including differentiation, cellular signaling, genomic imprinting, alternative splicing, angiogenesis, epigenetic regulation, cell death, cell proliferation, and growth [7, 8]. Increasing evidence has indicated that dysregulation in expression levels of many lncRNAs are associated with developmental processes and disease states most notably in cancer [7, 17].
One of the first reported and characterized lncRNAs involved in cancer progression and associated with metastasis was HOTAIR [6, 8, 21–23]. HOTAIR was originally discovered by Rinn et al. through a custom tilling array of the HOXC locus (12q13.13) [18, 24, 25]. Several studies assessed the relative expression of HOTAIR in different cancers, such as breast cancer [7, 11, 16, 17, 23], liver cancer , non-small-cell lung cancer (NSCLC) [7, 26], colorectal cancer [17, 27], gastrointestinal stromal tumor [7, 17, 28] and pancreatic cancer [7, 17, 29]. Moreover, HOTAIR is proposed to increase tumor invasiveness and metastasis [7, 17, 23]. The relative HOTAIR overexpression was reported and was shown to affect the tumor behavior in these cancers [7, 10, 11, 16, 17, 23, 26–29]. Furthermore, Gupta RA et al. showed high upregulation of HOTAIR in both primary and metastatic breast tumors . Correlations between overexpression of HOTAIR in HCC and different clinicopathological factors including larger tumor size, lymph node metastasis, tumor recurrence after liver transplantation (LT), and shorter disease-free survival after surgical resection (DFS) or LT has been reported [10, 18, 30, 31]. HOTAIR lncRNA can increase the carcinogenic activity of HCC cells by interacting with tumor suppressor microRNAs and suppressing the RNA binding motif protein, hence accelerating the epithelial-mesenchymal transition .
One of the long intergenic non-coding RNA (lincRNA) is MALAT1 with >8,000 nts, located on chromosome 11q13 . MALAT1 is correlated with high metastatic potential and poor patient prognosis in a variety of cancers, such as lung cancer, hepatocellular carcinoma, breast, prostate, uterus, and esophageal squamous [4, 6, 12, 33]. This lncRNA is associated with cancer in terms of proliferation, metastasis, invasion, and apoptosis . Association between high expression of MALAT1 and melanoma metastasis has been reported by Tian et al . Moreover, Dong et al. revealed that MALAT1 can play an important role in tumor proliferation and metastasis via the phosphoinositide 3-kinase (PI3K)/Akt pathway . It has been shown that overexpression of MALAT1 in tumor tissues or sera may cause advanced tumor stages and reduced overall survival of HCC patients and can signify a higher risk of tumor recurrence following liver transplantation [3, 36]. In addition, the correlation between overexpression of MALAT1 in HCC and chemoresistance to multiple agents including 5-fluorouracil, mitomycin C, and Adriamycin via a hypoxia-inducible factor (HIF)-1α-MALAT1-microRNA(mir)-216b pathway has been reported . Also, the key role of MALAT1 in HCC progression by inducing serine/arginine-rich splicing factor 1 (SRSF1) upregulation and mammalian target of rapamycin (mTOR) activation was demonstrated .
UCA1 gene is placed in chromosome 19p13.12, having three exons and encoding two transcripts. In several studies upregulation of UCA1 in some cancers including bladder cancer, breast cancer, colorectal cancer, prostate cancer, and osteosarcoma has been shown [15, 39–43]. Alireza Fotouhi Ghiam et al. reported the important role of UCA1 as one of significant mediators of radiation response in prostate cancer . Moreover, according to Wen et al. UCA1 can perform as a potential biomarker for diagnosis and prognosis of osteosarcoma . Ultimately, Wang et al. revealed the significance of UCA1 in predicting tumor lymph node metastasis . According to Feng Wang et al. UCA1 overexpression in HCC tissues has been linked to a variety of factors, including TNM stage, metastasis, and postoperative survival. UCA1 has the ability to reverse the inhibitory effect of miR-216b on HCC cell growth and metastasis, which could be related to the derepression of fibroblast growth factor receptor 1 (FGFR1) expression acting as a miR-216b target gene and the activation of the ERK signaling pathway .
In this study, we first assessed the expression of HOTAIR, MALAT1, and UCA1 in liver cancer tissues. From the results obtained in our study, HOTAIR, MALAT1, and UCA1 lncRNA in liver cancer tissues showed to have increased expression levels compared to the healthy tissues. Our findings are in agreement with previous study studies [4, 8, 15, 18]. In various reports, significant correlations between HOTAIR, MALAT1, and UCA1 expression levels and clinical-pathological characteristics, such as lymph node metastasis, clinical stage, and tumor size, in some cancers including gastric cancer , HCC , ESCC , and osteosarcoma  were found. However, our results did not show significant correlations between HOTAIR, MALAT1, and UCA1 expression levels and the clinical-pathological characteristics, our findings also indicated HOTAIR, MALAT1, and UCA1 can serve as a biomarker for the diagnosis of liver cancer. According to various studies HOTAIR, MALAT1, and UCA1 may be as a biomarker in gastric cancer, papillary thyroid cancer, and osteosarcoma, respectively [13, 40, 45]. Our findings are in line with these studies. Some studies have reported significant relationships between OS and the relative expression of these lncRNAs (HOTAIR, MALAT1, and UCA1) [4, 12, 15, 18, 33], but the OS of patients with high expression of these lncRNAs in liver cancer tissues was not significantly lower in our investigation.