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Long non-coding RNA KTN1-AS1 promotes progression in pancreatic cancer through regulating
1Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.
Abstract:
To explore the inhibitory effect of long non-coding RNA (LncRNA) antisense of KTN1 (KTN1-AS1) on the growth of pancreatic cancer (PC) cells by regulating the microRNA-23b-3p (miR-23b-3p)/high-mobility group box 2 (HMGB2) axis. The expression of KTN1-AS1 in tissues and cells was detected by qRT-PCR, and the relationship between KTN1-AS1 and clinicopathological data of patients with PC was analyzed. In addition, stable and transient overexpression and inhibition vectors were established and transfected into PC cells PANC-1, BxPC-3. CCK-8, transwell, and flow cytometry were responsible for the detection of proliferation, invasion, and apoptosis of transfected cells, respectively. The correlation of miR-23b-3p between KTN1-AS1 and HMGB2 was determined by dual luciferase reports, and the relationship between KTN1-AS1 and miR-23b-3p was further verified by RNA immunoprecipitation (RIP). The highly expressed KTN1-AS1 in PC patients was indicative of its high diagnostic value in this disease. Besides, it was found that KTN1-AS1 was linked with the pathological stage, differentiation degree and lymph node metastasis (LNM) of PC patients. Underexpressed KTN1-AS1 led to decreased proliferation and invasion ability of cells and increased apoptosis rate, while the effect of further overexpression of KTN1-AS1 on cells was the opposite. Dual luciferase reporter (DLR) assay confirmed that KTN1-AS1 could target miR-23b-3p, while miR-23b-3p could target HMGB2. Functional analysis showed that the overexpression of miR-23b-3p inhibited the expression of HMGB2 in PC cells and affected cell proliferation, invasion and apoptosis. Co-transfection of Sh-KTN1-AS1 and miR-23b-3p-mimics exhibited that up-regulation of KTN1-AS1 expression could reverse the effect of miR-23b-3p-mimics on PC cells.
Insights
Long non-coding RNA KTN1-AS1 promotes pancreatic cancer growth by inhibiting miR-23b-3p, which targets HMGB2. This discovery offers a potential diagnostic and therapeutic target for pancreatic cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Pancreatic cancer (PC) remains a significant health challenge with limited therapeutic options.
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer development and progression.
- Understanding the molecular mechanisms underlying PC pathogenesis is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of lncRNA KTN1-AS1 in pancreatic cancer progression.
- To elucidate the regulatory axis involving KTN1-AS1, microRNA-23b-3p (miR-23b-3p), and high-mobility group box 2 (HMGB2) in PC cells.
- To assess the diagnostic and prognostic value of KTN1-AS1 in pancreatic cancer.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to detect KTN1-AS1 expression.
- Cell proliferation, invasion, and apoptosis assays (CCK-8, Transwell, flow cytometry) in transfected PC cells.
- Dual-luciferase reporter assays and RNA immunoprecipitation (RIP) to confirm molecular interactions.
Main Results:
- KTN1-AS1 was highly expressed in PC tissues and correlated with advanced clinicopathological features, including lymph node metastasis.
- Downregulation of KTN1-AS1 inhibited PC cell proliferation and invasion while promoting apoptosis.
- KTN1-AS1 directly targeted miR-23b-3p, and miR-23b-3p targeted HMGB2, suggesting a regulatory axis.
- Overexpression of miR-23b-3p reversed the oncogenic effects of KTN1-AS1.
Conclusions:
- KTN1-AS1 acts as an oncogenic lncRNA in pancreatic cancer by sponging miR-23b-3p and upregulating HMGB2.
- KTN1-AS1 holds potential as a diagnostic biomarker and therapeutic target for pancreatic cancer.
- The KTN1-AS1/miR-23b-3p/HMGB2 axis represents a novel regulatory pathway in pancreatic cancer progression.
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