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Long noncoding RNA SNHG14 accelerates cell proliferation, migration, invasion and suppresses apoptosis in colorectal
1Department of Gastroenterology Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. ni1967829e@126.com.
Objective:
Colorectal cancer (CRC) is a gastrointestinal tract cancer, which threatens the well-being of million of patients due to high metastasis. Recently, numerous studies have recognized nuclear RNA host gene 14 (SNHG14) as a remarkable oncogene in different cancers. However, the regulatory mechanism of SNHG14 in CRC development is mostly unclear.
Patients And Methods:
The expression of SNHG14, miR-944 and Kirsten rat sarcoma (KRAS) in tissues and cells was measured by quantitative Real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis were evaluated by cell counting kit-8 (CCK-8) and flow cytometry assay, respectively. Cell migration and invasion were assessed using transwell assay. Protein expression of KRAS, AKT, phosphorylated AKT (p-AKT), phosphatidylinositol-3-kinase (PI3K) and phosphorylated PI3K (p-PI3K) was detected by Western blot. Animal models were constructed by subcutaneously injecting SW620 cells stably transfected with sh-SNHG14 and sh-NC. The interaction among SNHG14, miR-944 and KRAS was determined by luciferase reporter assay and RIP assay.
Results:
The expression of SNHG14 and KRAS was up-regulated whereas miR-944 was down-regulated in CRC tumors and cells compared with normal tissues and cells. In addition, SNHG14 silencing attenuated cell proliferation, migration and invasion, while accelerated apoptosis in CRC cells by suppressing PI3K/AKT pathway. Consistently, SNHG14 knockdown hindered tumor growth in vivo. MiR-944 was a target of SNHG14 and directly targeted KRAS. Moreover, miR-944 inhibitor abrogated silenced SNHG14-mediated inhibition on proliferation, migration and invasion, as well as promotion on apoptosis in CRC cells. Similarly, miR-944 regulated CRC cell progression by targeting KRAS through PI3K/AKT pathway.
Conclusions:
SNHG14 contributed to cell proliferation, migration and invasion, while suppressed apoptosis in CRC cells by targeting miR-944/KRAS axis through PI3K/AKT pathway, representing novel biomarkers for CRC therapy.
Insights
The long non-coding RNA SNHG14 promotes colorectal cancer (CRC) progression by targeting miR-944 and KRAS, impacting the PI3K/AKT pathway. This finding offers potential new biomarkers for CRC therapy.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- Colorectal cancer (CRC) is a significant global health concern, characterized by high metastasis rates.
- The role of nuclear RNA host gene 14 (SNHG14) as an oncogene is recognized, but its specific regulatory mechanism in CRC remains largely unknown.
Purpose of the Study:
- To elucidate the regulatory mechanism of SNHG14 in colorectal cancer development.
- To investigate the interaction between SNHG14, miR-944, and KRAS in CRC.
Main Methods:
- Quantitative Real-Time PCR (qRT-PCR) and Western blotting were used to assess gene and protein expression.
- Cell viability, apoptosis, migration, and invasion assays (CCK-8, flow cytometry, Transwell) were performed.
- In vivo tumor growth was evaluated in animal models, and molecular interactions were confirmed via luciferase reporter and RIP assays.
Main Results:
- SNHG14 and KRAS were upregulated, while miR-944 was downregulated in CRC tissues and cells.
- SNHG14 silencing inhibited CRC cell proliferation, migration, and invasion, and promoted apoptosis by suppressing the PI3K/AKT pathway.
- MiR-944 directly targeted KRAS, and its inhibition reversed the effects of SNHG14 silencing on CRC cells.
Conclusions:
- SNHG14 promotes CRC cell proliferation, migration, and invasion while suppressing apoptosis.
- The SNHG14/miR-944/KRAS axis regulates CRC progression via the PI3K/AKT pathway.
- SNHG14 represents a potential novel biomarker for CRC diagnosis and therapy.
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