Gastric cancer is one of the most dangerous and fatal cancers in the world, which is ranked third in terms of the deadliest among all types of neoplasms. This type of neoplasm is increasing in the world today, and different cognitive ways have been expressed. However, extensive studies are required to identify and cure it [17, 18].
Long non-coding RNAs (lncRNAs) contribute greatly in many diseases, for example cancer. Genomic studies of transcriptomes (a study of all coding and non-coding RNAs) have shown that transcription is abundant in the mammalian genome, which at least 80% of this transcription is exclusively related to non-coding RNAs (ncRNAs) . ncRNAs are classified into two groups based on their sequencing length: short ncRNAs with less than 200 nucleotides (sncRNAs) and long non-coding RNAs with more than 200 nucleotides (lncRNAs). Until now, according to numerous studies, more than 58,000 lncRNAs have been identified in the human genome. A large number of lncRNAs have not been found to function and role and they seem to act only as transcriptional noises. However, some of them have different functions in gene transcription and protein translation. Unlike microRNAs, lncRNAs are able to activate the gene expression and others have the ability to suppress it. lncRNAs are able to interact with a variety of macromolecules, such as DNA, RNA, and proteins, and play vital roles in regulating gene expression at transcriptional, post transcriptional and epigenetic levels. lncRNAs are mainly located within the nucleus and affect the expression of gene at the epigenetic level, and a small number (approximately 15%) are present in the cytoplasm and regulate protein translation. An important role of lncRNAs in many diseases, especially cancer, has been reported in numerous studies . Recently, a number of lncRNAs have proven to play a significant part in the proliferation, cell cycle, apoptosis, invasion, migration, metastasis and tumorigenicity of gastric cancer cells . As previously mentioned, less than thousands of lncRNA mechanisms have been discovered. Recently, three lncRNAs have been identified including TPT1-AS1, SAMMSON and LINC00961, which have been subjected to limited studies on their action mechanism in cancer.
TPT1-AS1 is one of the most recent lncRNAs that is located on the 13q14.13 gene. This lncRNA has recently been investigated in glioma and cervical cancer. It is observed that increased expression of this lncRNA can enhance the tumor size, proliferation, metastasis, and requires treatments that are more difficult. . On the other hand, this lncRNA is associated with a protein called SP1 . SP1 along with zinc finger protein 179 (ZnF 179) create a route which can affect the protection against oxidative stress and mitochondria-induced ROS. This protein is one of the factors involved in transcription and also regulates the expression of some subunits in the complex of electron transport chain . It has been observed that overexpression of TPT1-AS1 can increase the expression of gene and SP1 protein, which eventually results in the disruption of the electron transfer chain, ultimately damaging the mitochondria and cells and exacerbating oxidative stress condition .
SAMMSON locus is located on the chromosome 3p13. This lncRNA is associated with the Wnt/B Catenin pathway. It has been shown that increased expression of this lncRNA can activate the pathway in cancerous cells and accelerate the growth of the cells, metastasis, and self-renewal of these cells . This lncRNA is also associated with a mitochondrial protein called P32, which is effective both in the integrity of the mitochondrial structure and in the production of energy through oxidative phosphorylation. It can also contribute to the progression of certain cancers and the transformation of the cell metabolism from oxidative phosphorylation to glycolysis and the increased oxidative stress, due to its ineffectiveness and lack of proper production . SAMMSON, as mentioned above, is associated with this protein, and by deactivating P32, it can disrupt the mitochondrial function and structure and also leads to an oxidative stress condition .
The ROC curve results showed a relatively appropriate specificity and sensitivity for SAMMSON and LINC00961 RNA levels in cancerous and non cancerous tissues, indicating that these two genes expression levels may be used for gastric cancer diagnosis.
As it is shown in our finding, overexpression of TPT1-AS1 and SAMMSON have a significant association with the advanced grades of cancerous tissues. According to the previous studies, increased expression of these lncRNAs may enhance the growth of the cancer cell and tumor tissue proliferation. It can be concluded that TPT1-AS1 and SAMMSON take a leading role in the development of gastric cancer, especially in the higher grades, and increased expression of these genes can be considered as a diagnosis pathway in gastric cancer. In the future, it can be used to treat this lethal cancer by inhibiting lncRNAs. On the other hand, increased expression of these genes can damage mitochondria and increase oxidative stress circumstance.
Another lncRNA, which has been investigated in this study, is LINC00961. This lncRNA, which is located on the 9p13.3 gene, significantly contribute in various cancer processes and has 1546 nucleotides. This lncRNA acts on a polypeptide called Small Regulatory Polypeptide of Amino Acid Response (SPAR), which can inhibit (mammalian Target Of Rapamycin Complex 1) mTORC1, but nevertheless this lncRNA can affect the activity of mTORC1, and this complex can also control mitochondria in electron transport chain complex proteins and ATP production and consumption . It is expected to modify the toxicity of mitochondrial oxidative stress and contribute to the onset of cancer. It has been shown that increased expression of LINC00961 can have an inhibitory role in the metastasis and proliferation of cancerous cells .
Based on the findings of the present study, a significant overexpression of TPT1-AS1 and SAMMSON in cancerous tissues has been shown in comparison with healthy adjacent tissues. On the other way, decreased expression of LINC00961 in patients with gastric cancer, as compared to the healthy adjacent group, revealed that in the pathologic condition, overexpression of TPT1-AS1 and SAMMSON and down expression of LINC00961 might take a leading role in the development of gastric cancer as well as in higher grades.
Recently, studies have been done to increase the expression of TPT1-AS1 gene, for example, in 2017, Jiang et al. studied cervical cancer both in vivo and in vitro, and observed that lncRNA TPT1-AS1 could be involved as an oncogenic agent in the development of cervical cancer, and also, they introduced it as an effective therapeutic goal . In addition, in 2019, Wu et al. studied epithelial ovarian cancer, and observed that lncRNA TPT1-AS1 could lead to tumorigenesis and metastasis in epithelial ovarian cancer .
In 2017, Li et al. Conducted a study on liver cancer both in vivo and in vitro, and found that SAMMSON lncRNA activates Wnt / B Catenin pathway in cancer cells and can activate these cells in their growth and self-renewal of cancer cells  .
In 2018, Huang et al. investigated the cancer tissues of patients with lung cancer and found that the expression of LINC00961 gene has declined significantly in these patients, and in healthy subjects, this lncRNA had an inhibitory effect on the cell growth, proliferation and metastasis . In 2019, Lixia Zhang et al. studied on the cancer tissues of patients with Tongue Squamous Cell Carcinoma (TSCC) and observed that the expression of LINC00961 has significantly decreased and this lncRNA, with its own function, inhibits the growth, proliferation and metastasis of cancerous cells by regulating the Wnt/β-Catenin signaling pathway .
Considering these functions of the lncRNAs mentioned above, if a mutation takes place in the expression of these lncRNAs, it could affect different signaling pathways. With the effect on various genes and proteins presented in these pathways, they can contribute to the progression, invasion and metastasis in cancerous cells, which is due to the increased expression of TPT1-AS1 and SAMMSON and reduced expression of LINC00961 [9, 11, 12]. In this study, using genetic techniques and biochemical tests, it has been found that overexpression of TPT1-AS1 and SAMMSON and down expression of LINC00961 could increase proliferation, invasion and metastasis in cancerous cells compared to healthy subjects. According to the previous studies and the present study, it can be concluded that these important lncRNAs may cause gastric cancer and can be used as tumor markers of this cancer. However, more research and large numbers of samples are required to reveal the exact mechanisms of this LncRNAs and better understanding of their potential use in gastric cancer.