The effects of long non code RNAs in pancreas cancer

We can divide the pancreatic cancer in two types first is caused by exocrine tumors that consider ۹۳ percent of the pancreatic cancer but the other ۷ percent is caused by Neuroendocrine Tumors (PNETs) . They are a type of RNA, generally defined as transcripts with more than ۲۰۰ nucleotides that are not transbay interacting with DNA, RNA and proteins, lncRNAs can modulate chromatin structure and function and the transcription of neighbouring and distant genes, and affect RNA splicing, stability and translation.[۳] the roles of lncRNAs in pancreatic cancers can be oncogenic or tumor suppressive. Major lncRNAs in pancreatic cancer : first oncogenics : ۱- HOTAIR : (HOX transcript antisense RNA) . could transcriptionally regulate the expression of hundreds of genes in both PRC۲-dependent and PRC۲-independent manner in pancreatic cancer cells.In conclusion, the present study demonstrated that HOTAIR may be induced by gemcitabine and acts as a tumor promoter by inhibiting the chemosensitivity, and promoting the self‑renewal capacity, proliferation and migration of PANC‑۱ CSCs, which supports its potential application as a novel therapeutic approach for pancreatic cancer.[۴,۵] ۲- MALAT-۱ : Metastasis-associated lung adenocarcinoma transcript ۱ (MALAT-۱) is highly conserved and ubiquitously expressed lncRNA. high expression of MALAT-۱ has been found in various cancer tissues including pancreatic cancer .[۶,۷] The researchs has shown that MALAT-۱ Promotes Chemoresistance via Modulating EMT and promoted aggressive pancreatic cancer proliferation and metastasis via stimulation of autophagy and its knockdown was shown to induce apoptosis and suppress cell migration and invasion in pancreatic cancer . ۳- H-۱۹ : H۱۹ is an oncogenic lncRNA which antagonizes tumor suppressive let-۷ [۸].Knockdown of H۱۹ in pancreatic cancer cells inhibited cell proliferation and tumor growth with G۰/G۱ arrest and downregulation of E۲F-۱ transcription factor . Knockdown of H۱۹ also inhibited metastasis of pancreatic cancer . ۴-PVT-۱ : The research has shown that Increased expression of the lncRNA PVT۱ is associated with poor prognosis in pancreatic cancer patients. PVT۱ also promoted autophagy and cell growth by regulating miR-۲۰a-۵p and ULK۱ signaling, leading to the development of pancreatic cancer. ۵- HOTTIP : HOXA transcript at the distal tip (HOTTIP) is another oncogenic lncRNA HOTTIP is located at the ۵′ end of HOXA cluster . It was found that ectopic HOTTIP expression promoted growth and invasiveness in pancreatic ductal adenocarcinoma . [۹] Here some of the tumor suppressive lncRNAs : ۱- GAS۵ : downregulation of GAS۵ increased cell proliferation by regulating CDK۶ transcriptionally, suggesting the tumor suppressive role of GAS۵. GAS۵ also reversed EMT, inhibited metastasis and increased the sensitivity of pancreatic cancer stem cells to gemcitabine through targeting miR-۲۲۱/SOCS۳ signaling . ۲- MEG۳ : expression levels of MEG۳ in both pancreatic cancer tissues and cells were found to be much lower than that in normal tissues and cells [۱۰]. Knockdown of MEG۳ promoted pancreatic cancer cell proliferation, migration, and invasion [۱۰] while overexpression of MEG۳ suppressed pancreatic neuroendocrine tumor cell viability, invasion, and migration . In addition, MEG۳ could also exert its anti-cancer effects on pancreatic cancer by regulation of the PI۳K/AKT signaling pathway.

کلیدواژه ها:

exocrine ، proliferation ، lncRNAs ، oncogenic ، gemcitabine