LINC00152 promotes proliferation in hepatocellular carcinoma by targeting EpCAM via the mTOR signaling pathway

Multidrug resistance (MDR) is a key to the ineffectiveness of hepatocellular carcinoma (HCC) chemotherapy. Oxaliplatin (OXA), as one of the first-line chemotherapeutic drugs for HCC, abnormally activates the PI3K/AKT/mTOR signaling pathway and DNA damage repair pathway (NHEJ and HR), causing drug resistance and consequnet compromised efficacy. Herein, we developed a hollow polydopamine nanoparticle (H-PDA)-based nano-delivery system (O/P-HP) that contained OXA and a dual PI3K/mTOR inhibitor PKI-587 with complementary effects for combating drug resistance in cancer chemotherapy. The hollow structure of H-PDA endowed O/P-HP with high loading efficiencies of OXA and PKI-587–up to 49.6% and 7.0%, respectively. In addition, benefiting from the intracellular delivery of H-PDA as well as the highly concentrated drugs therein, O/P-HP inhibited the proliferation of OXA-resistant HR cells, resulting in a cell viability of only 17.63%. These values were significantly superior to those with OXA single-agent treatment and treatment with free OXA in combination with PKI-587. We examined the intrinsic mechanisms of the combination therapy: O/PHP had excellent anti-cancer effects via the simultaneous upstream and downstream action to re-sensitize HR cells to chemotherapy; OXA induced strong apoptosis via the direct platinum lesions on DNA molecules, while PKI-587 normalized the abnormally activated PI3K/AKT/mTOR signaling pathway and DNA damage repair pathway (NHEJ and HR) that could attenuate the effectiveness of OXA, thus resulting in inhibition of cell proliferation, migration and DNA repair enzyme activity and the augment of apoptotic effects. Such combination therapy, with simultaneous upstream and downstream action, may be a strategy for minimizing resistance for anti-cancer treatments.

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LncRNA TMPO‐AS1 promotes hepatocellular carcinoma cell proliferation, migration and invasion through sponging miR‐329‐3p to stimulate FOXK1‐mediated AKT/mTOR signaling pathway

Cancer Medicine ◽

10.1002/cam4.3046 ◽

2020 ◽

Vol 9 (14) ◽

pp. 5235-5246 ◽

Cited By ~ 2

Author(s):

Xiaobo Guo ◽

Yun Wang

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Signaling Pathway ◽

Carcinoma Cell ◽

Mtor Signaling ◽

Migration And Invasion ◽

Mtor Signaling Pathway ◽

Hepatocellular Carcinoma Cell

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Upregulated UCA1 contributes to oxaliplatin resistance of hepatocellular carcinoma through inhibition of miR‐138‐5p and activation of AKT/mTOR signaling pathway

Pharmacology Research & Perspectives ◽

10.1002/prp2.720 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Guolin Huang ◽

Li Li ◽

Chaoyong Liang ◽

Fei Yu ◽

Cuifang Teng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Signaling Pathway ◽

Mtor Signaling ◽

Mtor Signaling Pathway

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Interferon-Induced Transmembrane Protein 3 Expression Upregulation Is Involved in Progression of Hepatocellular Carcinoma

BioMed Research International ◽

10.1155/2021/5612138 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Yuli Hou ◽

Shanshan Wang ◽

Mengdan Gao ◽

Jing Chang ◽

Jianping Sun ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Signaling Pathway ◽

Transmembrane Protein ◽

Metastatic Potential ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

Cell Proliferation And Migration ◽

And Migration ◽

Proliferation And Migration

Purpose. Interferon-induced transmembrane protein 3 (IFITM3) is a key signaling molecule regulating cell growth in some tumors, but its function and mechanism in hepatocellular carcinoma (HCC) remain unknown. Our study investigated the relationship between the expression of IFITM3 and HCC development. Material and Methods. IFITM3 expression was identified via multiple gene expression databases and investigated in HCC tissue samples. Then, PLC/PRF/5 cells were transfected with lentivirus to knock down and overexpress the expression of IFITM3. IFITM3 expression, cell proliferation, and migration were detected by qRT-PCR, western blotting, QuantiGene Plex 2.0 assay, immunohistochemistry, CCK-8, and wound healing tests. RNA-seq technology identified the PI3K/AKT/mTOR pathway as an IFITM3-related signaling pathway for investigation. Results. IFITM3 expression was higher in HCC tissues than in adjacent normal tissues, and the level of IFITM3 was higher in HCC tissues with low differentiation and metastatic potential than in those with high/medium differentiation and without metastatic potential. A higher RNA level of IFITM3 was found in samples with IFITM3 rs12252-CC genotype rather than the TT genotype. Knockdown of IFITM3 in PLC/PRF/5 cells inhibited cell proliferation and migration, blocked the expression of the PI3K/AKT/mTOR signaling pathway, and decreased the expression of vimentin. The results were opposite with the overexpression of IFITM3. Conclusion. Upregulation of IFITM3 plays a role in the development of HCC. Possibly through regulating HCC cell proliferation and migration, these effects are associated with the PI3K/AKT/mTOR signaling pathway. Upregulation of IFITM3 is also associated with the IFITM3 rs12252-CC genotype.

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MiR-92a-3p promotes the malignant progression of hepatocellular carcinoma by mediating the PI3K/AKT/mTOR signaling pathway

Current Pharmaceutical Design ◽

10.2174/1381612827666210612054156 ◽

2021 ◽

Vol 27 ◽

Author(s):

Libing Wang ◽

Mingxin Cui ◽

Fengzhi Qu ◽

Daming Cheng ◽

Jingkun Yu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Western Blot ◽

Signaling Pathway ◽

Epithelial Mesenchymal Transition ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

Mesenchymal Transition ◽

Diagnosis And Prognosis ◽

Potential Biomarker ◽

Hcc Cells

Background: As one of the most common cancers in the world, hepatocellular carcinoma (HCC) usually has a poor prognosis. Many HCC patients are usually diagnosed at advanced stages. Therefore, new potential biomarkers for the diagnosis and prognosis of HCC are urgently needed. More and more studies have shown that miR-92a-3p can regulate the occurrence and development of a variety of cancers, but its clinical significance and molecular mechanism in HCC are still elusive. Here, we tried to clarify the regulatory mechanism of miR-92a-3p in HCC. Methods: In this study, we conducted qRT-PCR and revealed that miR-92a-3p was notably upregulated in HCC cells. MTT, flow cytometry, wound healing, Transwell invasion assays and western blot were conducted to uncover that overexpressed miR-92a-3p could boost the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells while inhibiting cell apoptosis. In addition, the proteins associated with PI3K/AKT/mTOR pathway were also detected by western blot. Results: It was suggested that miR-92a-3p could activate the PI3K/AKT/mTOR signaling pathway. Conclusion: These results suggest that miR-92a-3p plays a tumor-promoting role in HCC and may be a potential biomarker for the diagnosis and prognosis of HCC.

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