The regulation and function of microRNA-377/RASSF8 signaling axis in gastric cancer

Abstract

Gastric cancer is a major cause of cancer-associated mortality worldwide. The aberrant expression of microRNA (miRNA) is involved in tumorigenesis. Ras proteins transfer information from the extracellular environment to internal cellular compartments and are essential in numerous signal transduction pathways. To investigate the regulation, function and clinical significance of the miRNA377/Ras association domain family (RASSF) 8 signaling axis in gastric cancer, reverse transcription-quantitative polymerase chain reaction, immunohistochemistry, cell counting kit-8, western blotting, and Transwell assays were used. The results revealed that expression of RASSF8 was significantly upregulated in normal gastric tissues compared with gastric cancer, which was further confirmed by immunohistochemical analysis, and its expression level was increased in normal gastric cells compared with gastric cancer cell lines. However, the expression of miR-377 was significantly upregulated in gastric cancer compared with normal gastric tissues. In addition, RASSF8 overexpression in BGC-823 gastric cancer cells significantly inhibited the proliferation, apoptosis and invasive abilities of cells. Whereas miR-377 attenuated these effects due to downregulated RASSF8 expression by directly targeting its 3′-untranslated region. Furthermore, in the current study, miR-377 was not able to reverse the effects of RASSF8 overexpression on gastric cancer cells. Collectively, the RASSF8 gene may represent a novel molecular target involved in gastric cancer development and may be useful in targeted therapy of patients with gastric cancer.

CircPRMT5 circular RNA promotes proliferation of colorectal cancer through sponging miR‐377 to induce E2F3 expression

“…MiR‐377, miR‐30c, miR‐188, miR‐335 and miR‐597 were reported to contain 1‐2 binding sites for the circPRMT5 region . Particularly, miR‐377 has been proved to be involved in the proliferation and metastasis of many types of tumours of digestive system . Therefore, we suggested that circPRMT5 can bind to miR‐377 in the progression of CRC.…”

“…11 Particularly, miR-377 has been proved to be involved in the proliferation and metastasis of many types of tumours of digestive system. [12][13][14][15] Therefore, we suggested that circPRMT5 can bind to miR-377 in the progression of CRC. Thus, the occupancy of Ago2 in the region of circPRMT5 was analysed by using RNA immunoprecipitation and showed that endogenous circPRMT5 pulled-down from Ago2 cells was specifically abounded, indicating that circPRMT5 could incorporate into the RNA-induced silencing complex in CRC ( Figure 3C).…”

Identification of microRNA editing sites in clear cell renal cell carcinoma

“…RASSF8 has been reported to be a tumor suppressor gene with lower expression in gastric cancer 96 , 97 , colorectal cancer 98 , 99 , cervical cancer 100 , ovarian cancer 101 , melanoma 102 , esophageal squamous cell carcinoma 103 , lung cancer 104 , 105 and osteosarcoma 106 . In addition, RASSF8 is a potential therapeutic target for the prevention of many cancers 97 , 100 , 103 , 105 .…”

Regulation of RASSF by non-coding RNAs in different cancers: RASSFs as masterminds of their own destiny as tumor suppressors and oncogenes

“…RASSF8 overexpression significantly inhibited the proliferation and invasive abilities of BGC-823 gastric cancer cells [ 76 ]. miR-377-mediated targeting of RASSF8 in gastric cancer cells.…”

“…miR-377-mediated targeting of RASSF8 in gastric cancer cells. RASSF8 overexpression caused significant suppression of the proliferation of BGC-823 cancer cells, whereas miR-377 abolished RASSF8-induced reduction in the proliferation properties of gastric cancer cells [ 76 ].…”