TSitologiya i Genetika 2023, vol. 57, no. 2, 62-64
Cytology and Genetics 2023, vol. 57, no. 2, 186–196, doi: https://www.doi.org/10.3103/S0095452723020032

A comprehensive genome-wide analysis of lncrna expression profile during hepatic carcinoma cell proliferation promoted by phospholipase Cγ2

Chen X., Lv Q., Liu Y.

  • Animal Science and Technology School, Henan University of Science and Technology, 263# Kaiyuan Avenue, Luoyang 471023, China

Phospholipase Cγ2 has a promotive effect on hepatic carcinoma development. Meanwhile, lncRNAs play a critical role in the pathology. Therefore, to determine whether phospholipase Cγ2 could enhance HCC cell proliferation by regulating lncRNA transcription, hepatic carcinoma cells RH35 were infected with Ad­phospholipase Cγ2 constructed previously, followed by lncRNA sequencing by high­throughput technology. Differently expressed lncRNAs (DElncRNAs) and their target genes were identified according to strict criteria. GO and KEGG, Reactome pathway analyses were performed to analyze biological processes and the related pathways of DElncRNAs. lncRNA/mRNA coexpression pairs were screened according to expression profiling combined with bioinformatics analysis. The results showed that 231 DElncRNAs were identified in Ad­phospholipase Cγ2­overexpressing cells compared to control, containing 60 up­ and 171 down­regulated ones. Target genes prediction analysis showed that 61 cis­ and 30 trans­acting DElncRNAs were matched to 55 and 26 targets, respectively. Coexpression analysis found 33 lncRNA/mRNA coexpression pairs including 24 pairs in cis. GO analysis showed that these cis­mode lncRNA/mRNA pairs were involved in cytoskeleton organization, cell adhesion, and multiple signaling pathways related to apoptosis, proliferation, and metastasis. Collectively, phospholipase Cγ2 caused significant alterations in the expression of many lncRNAs in liver cancer cells, providing valuable insight into the precise mechanism of phospholipase Cγ2­promoting liver cancer cell growth.

Keywords: phospholipase Cγ2; hepatic carcinoma; lncRNA transcriptome; bioinformatic analysis

TSitologiya i Genetika
2023, vol. 57, no. 2, 62-64

Current Issue
Cytology and Genetics
2023, vol. 57, no. 2, 186–196,
doi: 10.3103/S0095452723020032

Full text and supplemented materials


Alzayady, K.J., Wang, L., Chandrasekhar, R., Wagner, L.E., Van Petegem, F., and Yule, D.I., Defining the stoichiometry of inositol 1,4,5-trisphosphate binding required to initiate Ca2+ release, Sci. Signaling, 2016, vol. 9, no. 422, p. ra35.

Arab, K., Park, Y.J., Lindroth, A.M., Schäfer, A., Oakes, C., Weichenhan, D., Lukanova, A., Lundin, E., Risch, A., Meister, M., Dienemann, H., Dyckhoff, G., Herold-Mende, C., Grummt, I., Niehrs, C., and Plass, C., Long noncoding RNA TARID directs demethylation and activation of the tumor suppressor TCF21 via GADD45A, Mol. Cell, 2014, vol. 55, no. 4, pp. 604–614.

Bettermann, K., Mehta, A.K., Hofer, E.M., Wohlrab, C., Golob-Schwarzl, N., Svendova, vol., Schimek, M.G., Stumptner, C., Thüringer, A., Speicher, M.R., Lackner, C., Zatloukal, K., Denk, H., and Haybaeck, J., Keratin 18-deficiency results in steatohepatitis and liver tumors in old mice: A model of steatohepatitis-associated liver carcinogenesis, Oncotarget, 2016, vol. 7, no. 45, pp. 73309–73322.

Carlsten, J.O., Zhu, X., López, M.D., Samuelsson, T., and Gustafsson, C.M., Loss of the Mediator subunit Med20 affects transcription of tRNA and other non-coding RNA genes 1in fission yeast, Biochim. Biophys. Acta, 2016, vol. 1859, no. 2, pp. 339–347.

Durso, D.F., Bacalini, M.G., Valle, Í.F., Pirazzini, C., Bonafé, M., Castellani, G., Faria, A.M., Franceschi, C., Garagnani, P., and Nardini, C., Aberrant methylation patterns in colorectal cancer: a meta-analysis, Oncotarget, 2017, vol. 8, no. 8, pp. 12820–12830.

El Khodiry, A., Afify, M., and El Tayebi, H.M., Behind the curtain of non-coding RNAs; long non-coding RNAs regulating hepatocarcinogenesis, World J. Gastroenterol., 2018, vol. 24, no. 5, pp. 549–572.

Feng, L., Reynisdóttir, I., and Reynisson, J., The effect of PLC-γ2 inhibitors on the growth of human tumour cells, Eur. J. Med. Chem., 2012, vol. 54, pp. 463–469.

Ganegoda, G.U., Li, M., Wang, W., and Feng, Q., Heterogeneous network model to infer human disease-long intergenic non-coding RNA associations, IEEE Trans. NanoBiosci., 2015, vol. 14, no. 2, pp. 175–183.

Gao, M., Zhong, A., Patel, N., Alur, C., and Vyas, D., High throughput RNA sequencing utility for diagnosis and prognosis in colon diseases, World J. Gastroenterol., 2017, vol. 23, no. 16, pp. 2819–2825.

Gong, C., Li, Z., Ramanujan, K., Clay, I., Clay, I., Zhang, Y., Lemire-Brachat, S., and Glass, D.J., A long non-coding RNA, LncMyoD, regulates skeletal muscle differentiation by blocking IMP2-mediated mRNA translation, Dev. Cell, 2015, vol. 34, no. 2, pp. 181–191.

Hu, L., Ye, H., Huang, G., Luo, F., Liu, Y., Liu, Y., Yang, X., Shen, J., Liu, Q., and Zhang, J., Long noncoding RNA GAS5 suppresses the migration and invasion of hepatocellular carcinoma cells via miR-21, Tumour Biol., 2016, vol. 37, no. 2, pp. 2691–2702.

Huynh, M.Q., Goßmann, J., Gattenlöehner, S., Klapper, W., Wacker, H.H., Ramaswamy, A., Bittner, A., Kaiser, U., and Neubauer, A., Expression and pro-survival function of phospholipase Cγ2 in diffuse large B-cell lymphoma, Leuk. Lymphoma, 2015, vol. 56, no. 4, pp. 1088–1095.

Kashi, K., Henderson, L., Bonetti, A., and Carninci, P., Discovery and functional analysis of lncRNAs: Methodologies to investigate an uncharacterized transcriptome, Biochim. Biophys. Acta, 2016, vol. 1859, no. 1, pp. 3–15.

Lattanzio, R., Piantelli, M., and Falasca, M., Role of phospholipase C in cell invasion and metastasis, Adv. Biol. Regul., 2013, vol. 53, no. 3, pp. 309–318.

Lebherz-Eichinger, D., Krenn, C.G., and Roth, G.A., Keratin 18 and heat-shock protein in chronic kidney disease, Adv. Clin. Chem., 2013, vol. 62, pp. 123–149.

Li, S.P., Xu, H.X., Yu, Y., He, J.D., Wang, Z., Xu, Y.J., Wang, C.Y., Zhang, H.M., Zhang, R.X., Zhang, J.J., Yao, Z., and Shen, Z.Y., LncRNA HULC enhances epithelial-mesenchymal transition to promote tumorigenesis and metastasis of hepatocellular carcinoma via the miR-200a-3p/ZEB1 signaling pathway, Oncotarget, 2016, vol. 7, no. 27, pp. 42431–42446.

Li, W.H., Zhou, Z.J., Huang, T.H., Guo, K., Chen, W., Wang, Y., Zhang, H., Song, Y.C., and Chang, D.M., Detection of OSR2, VAV3, and PPFIA3 Methylation in the Serum of Patients with Gastric Cancer, Dis. Markers, 2016, vol. 2016, p. 5780538.

Li, Y., Ren, M., Zhao, Y., Lu, X., Wang, M., Hu, J., Lu, G., and He, S., MicroRNA-26a inhibits proliferation and metastasis of human hepatocellular carcinoma by regulating DNMT3B-MEG3 axis, Oncol. Rep., 2017, vol. 37, no. 6, pp. 3527–3535.

Lin, H.Y., Glinsky, G.V., Mousa, S.A., and Davis, P.J., Thyroid hormone and anti-apoptosis in tumor cells, Oncotarget, 2015, vol. 6, no. 17, pp. 14735–14743.

Luo, K., Li, Y., Yin, Y., Li, L., Wu, C., Chen, Y., Nowsheen, S., Hu, Q., Zhang, L., Lou, Z., and Yuan, J., USP49 negatively regulates tumorigenesis and chemoresistance through FKBP51-AKT signaling, EMBO J., 2017, vol. 36, no. 10, pp. 1434–1446.

Ogasawara, S., Komuta, M., Nakashima, O., Akiba, J., Tsuneoka, M., and Yano, H., Accelerated expression of a Myc target gene Mina53 in aggressive hepatocellular carcinoma, Hepatol. Res., 2010, vol. 40, no. 3, pp. 330–336.

Pertea, M., Pertea, G.M., Antonescu, C.M., Chang, T.C., Mendell, J.T., and Salzberg, S.L., String Tie enables improved reconstruction of a transcriptome from RNA-seq reads, Nat. Biotechnol., 2015, vol. 33, pp. 290–295.

Poss, Z.C., Ebmeier, C.C., and Taatjes, D.J., The Mediator complex and transcription regulation, Crit. Rev. Biochem. Mol. Biol., 2013, vol. 48, no. 6, pp. 575–608.

Qin, H., Lu, S., Thangaraju, M., and Cowell, J.K., Wasf3 deficiency reveals involvement in metastasis in a mouse model of breast cancer, Am. J. Pathol., 2019, vol. 189, pp. 2450–2458.

Quinn, J.J. and Chang, H.Y., Unique features of long non-coding RNA biogenesis and function, Nat. Rev. Genet., 2016, vol. 17, no. 1, pp. 47–62.

Reynisson, J., Jaiswal, J.K., Barker, D., D’mello, S.A., Denny, W.A., Baguley, B.C., and Leung, E.Y., Evidence that phospholipase C is involved in the antitumour action of NSC768313, a new thieno[2,3-b]pyridine derivative, Cancer Cell Int., 2016, vol. 16, p. 18.

Sahu, A., Singhal, U., and Chinnaiyan, A.M., Long noncoding RNAs in cancer: from function to translation, Trends Cancer, 2015, vol. 1, no. 2, pp. 93–109.

Shi, Y., Song, Q., Yu, S., Hu, D., and Zhuang, X., Microvascular invasion in hepatocellular carcinoma overexpression promotes cell proliferation and inhibits cell apoptosis of hepatocellular carcinoma via inhibiting miR-199a expression, OncoTargets Ther., 2015, vol. 8, pp. 2303–2310.

Sui, J., Yang, X., Qi, W., Guo, K., Gao, Z., Wang, L., and Sun, D., Long non-coding RNA Linc-USP16 functions as a tumour suppressor in hepatocellular carcinoma by regulating PTEN expression, Cell Physiol. Biochem., 2017, vol. 44, no. 3, pp. 1188–1198.

Sun, Y., Gao, X., Wu, P., Wink, M., Li, J., Dian, L., and Liang, Z., Jatrorrhizine inhibits mammary carcinoma cells by targeting TNIK mediated Wnt/β-catenin signalling and epithelial-mesenchymal transition (EMT), Phytomedicine, 2019, vol. 63, p. 153015.

Tang, L., Liang, Y., Xie, H., Yang, X., and Zheng, G., Long non-coding RNAs in cutaneous biology and proliferative skin diseases: Advances and perspectives, Cell Proliferation, 2020, vol. 53, p. e12698.

Teng, Y., Pi, W., Wang, Y., and Cowell, J.K., WASF3 provides the conduit to facilitate invasion and metastasis in breast cancer cells through HER2/HER3 signaling, Oncogene, 2016, vol. 35, pp. 4633–4640.

Vasuri, F., Visani, M., Acquaviva, G., Brand, T., Fiorentino, M., Pession, A., Tallini, G., D’Errico, A., and de Biase, D., Role of microRNAs in the main molecular pathways of hepatocellular carcinoma, World J. Gastroenterol., 2018, vol. 24, no. 25, pp. 2647–2660.

Vodopiutz, J., Schmook, M.T., Konstantopoulou, V., Plecko, B., Greber-Platzer, S., Creus, M., Seidl, R., and Janecke, A.R., MED20 mutation associated with infantile basal ganglia degeneration and brain atrophy, Eur. J. Pediatr., 2015, vol. 174, no. 1, pp. 113–118.

Wang, F., Yuan, J.H., Wang, S.B., Yang, F., Yuan, S.X., Ye, C., Yang, N., Zhou, W.P., Li, W.L., Li, W., and Sun, S.H., Oncofetal long noncoding RNA PVT1 promotes proliferation and stem cell-like property of hepatocellular carcinoma cells by stabilizing NOP2, Hepatology, 2014, vol. 60, pp. 1278–1290.

Wege, H., Li, J., and Ittrich, H., Treatment Lines in Hepatocellular Carcinoma, Visc. Med., 2019, vol. 35, no. 4, pp. 266–272.

Wu, S.X., Zhang, J.R., Liu, B.H., Huang, Y.J., Li, S.P., Wen, H.S., Zhang, M.Z., Li, J.F., Li, Y., and He, F., Identification and characterization of lncRNAs related to the muscle growth and development of Japanese flounder (Paralichthys olivaceus), Front. Genet., 2020, vol. 11, p. 1034.

Yang, F., Huo, X.S., Yuan, S.X., Zhang, L., Zhou, W.P., Wang, F., and Sun, S.H., Repression of the long noncoding RNA-LET by histone deacetylase 3 contributes to hypoxia-mediated metastasis, Mol. Cell, 2013, vol. 49, no. 6, pp. 1083–1096.

Yao, M., Yao, D.F., Bian, Y.Z., Zhang, C.G., Qiu, L.W., Wu, W., Sai, W.L., Yang, J.L., and Zhang, H.J., Oncofetal antigen glypican-3 as a promising early diagnostic marker for hepatocellular carcinoma, Hepatobiliary Pancreat Dis. Int., 2011, vol. 10, no. 3, pp. 289–294.

Ye, J., Tan, L., Fu, Y., Xu, H., Wen, L., Deng, Y., and Liu, K., LncRNA SNHG15 promotes hepatocellular carcinoma progression by sponging miR-141-3p, J. Cell. Biochem., 2019, vol. 120, no. 12, pp. 19775–19783.

Yuan, S.X., Long noncoding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients' poor recurrence-free survival after hepatectomy, Hepatology, 2012, vol. 56, no. 6, pp. 2231–2241.

Yuan, J.H., Yang, F., Wang, F., Ma, J.Z., Guo, Y.J., Tao, Q.F., Liu, F., Pan, W., Wang, T.T., Zhou, C.C., Wang, S.B., Wang, Y.Z., Yang, Y., Yang, N., Zhou, W.P., Yang, G.S., and Sun, S.H., A long noncoding RNA activated by TGF-β promotes the invasion-metastasis cascade in hepatocellular carcinoma, Cancer Cell, 2014, vol. 25, no. 5, pp. 666–681.

Zhang, G., Duan, A., Zhang, J., and He, C., Genome-wide analysis of long non-coding RNAs at the mature stage of sea buckthorn (Hippophae rhamnoides Linn) fruit, Gene, 2017, vol. 596, pp. 130–136.

Zhu, J., Liu, S., Ye, F., Shen, Y., Tie, Y., Zhu, J., Wei, L., Jin, Y., Fu, H., Wu, Y., and Zheng, X., Long noncoding RNA MEG3 interacts withp53 protein and regulates partial p53 target genes in hepatoma cells, PLoS One, 2015, vol. 10, no. 10, p. e0139790.